Phthalate Di-isodecyl & Di-isononyl phthalates

6. Do DIDP and DINP pose risks to human health?

• 6.1 Are workers at risk from exposure to DIDP and DINP?
• 6.2 Are consumers at risk from exposure to DIDP and DINP?

6.1 Are workers at risk from exposure to DIDP and DINP?

The source document for this Digest states:

DIDP

Workers

For the dermal route, the worst case for external skin exposure is considered to occur when 5 mg/cm2 of pure DIDP is applied during 8 hours on a skin surface of 840 cm2 (for both hands), then, for worst-case situations, it is proposed to take a maximum dermal intake of 2.4 mg/day equivalent to 0.03 mg/kg/day for a 70-kg man. For the inhalation route, the corresponding internal doses are calculated assuming 10 m3 of air inhaled in an 8-hour working day by a 70-kg worker and a 75% pulmonary absorption rate. The MOSs have to be determined for route-specific as well as combined inhalation and dermal exposure. As internal exposure by dermal route is very low, much lower than by inhalation route, the most significant contribution to the conclusions is via inhalation.

Considering the estimated combined internal exposure and comparing the NOAELs (15 mg/kg/d in dogs and 60 mg/kg/d in rats for hepatic effects), the MOSs have been calculated. For the occupational exposure, these MOSs are considered sufficient since the NOAEL was based on very slight effects (increase of relative liver weights in female rats at the higher dose). For offspring survival, considering the estimated combined internal exposure and comparing with the NOAELs of 33 mg/kg/d (slight decrease of survival indices in the F2 generation at higher doses), the MOSs have been calculated and are considered quite sufficient for the occupational exposure. For developmental effects, the MOSs have also been calculated, considering the estimated combined internal exposure and the relevant NOAEL of 500 mg/kg/d (skeletal variations in developmental rat studies) and the NOAEL of 263 mg/kg/d (decrease body weight in rat); for both effects, the MOSs are considered sufficient for the occupational exposure.

Conclusion (ii).

Source & ©: ECB "2003 Risk Assessment Report (RAR 041) on
Di-"isodecyl" Phthalate (DIDP), Summary of the Report, chapter 4: Human Health

DINP

Repeated dose toxicity (RDT) and reproductive effects are considered to be the critical endpoints in the risk assessment of DINP.

Risk characterisation

Workers

For the dermal route, the worst case for external skin exposure is considered to occur when 5 mg/cm2 of pure DINP is applied during 8 hours on a skin surface of 840 cm2 (for both hands), then, for worst-case situations, it is proposed to take a maximum dermal intake of 2.4 mg/day equivalent to 0.03 mg/kg/day for a 70-kg man. For the inhalation route, the corresponding internal doses are calculated assuming 10 m3 of air are inhaled in a 8-hour working day by a 70-kg worker and a 75% pulmonary absorption rate. The MOSs have to be determined for route-specific as well as combined inhalation and dermal exposure. As internal exposure by the dermal route is very low, much lower than by inhalation route, the most significant contribution to the conclusions is via inhalation.

Considering the estimated combined internal exposure and comparing the NOAELs of 88 mg/kg/d for hepatic effects and of 88 mg/kg/d for kidney effects in rats, the MOSs have been calculated. For the occupational exposure, these MOSs can be considered acceptable. For fertility (testicular effects) and offspring survival, considering the estimated combined internal exposure and comparing the NOAELs of 622 mg/kg/d (decrease of live birth and survival indices in the one-generation rat study) and of 276 mg/kg/d (testicular effects in mice in a 104-week study), the MOSs have been calculated and are considered quite sufficient for the occupational exposure. For developmental effects, the MOSs have also been calculated, considering the estimated combined internal exposure and the relevant NOAEL of 500 mg/kg/d (skeletal variations in developmental rat studies) and the LOAEL of 159 mg/kg/d (decrease offspring body weight in the 2-generation rat study); for both effects, the MOSs are considered sufficient for the occupational exposure.

Conclusion (ii).

Source & ©: ECB "2003 Risk Assessment Report (RAR 046) on
Di-"isodecyl" Phthalate (DIDP), Summary of the Report, chapter 4: Human Health

For more information, see the full ECB Risk Assessment Report:
 Chapter 4: Human Health

The same information on

6.2 Are consumers at risk from exposure to DIDP and DINP?

The source document for this Digest states:

DIDP

Consumers

As DIDP is present in several end products available to consumers, especially those in soft- PVC, consumer exposure can occur from various sources by different routes (inhalation, dermal, oral) in different situations.

Scenarios were built for three sub-populations:

Adults and children 3-15 years old

The MOSs are calculated for multiple exposure pathways and include exposure from the four scenarios (Building materials and furniture / Clothes, gloves and footwears / Car and public transport interior / Food and food-related uses). For all endpoints the MOSs are considered sufficient to protect adult consumers. Conclusion (ii).

Infants 6 months to 3 years old

Four exposure scenarios are considered as important for infants and newborns: Toys and baby equipment (foreseeable situation) / Building material and furniture / Food and food-related uses / Car and public transport interior. The MOSs are calculated in two ways: with or without toys exposure.

For repeated dose toxicity, the MOSs are considered sufficient to protect infants, except for the scenario with toys, based on the repeated dose toxicity dog study. So, in case DIDP should be a substitute for other phthalates in toys in the future, the MOS of 33, derived from hepatic toxicity in dog, would not be considered sufficient to protect infants. Conclusion (iii). Pertaining to reduced offspring survival (trans-generational effect observed in a two- generation rat study), in any case, owing to the uncertainty on the applicability of the NOAEL (16.5 mg/kg bw/d in rats) and the significance of the MOSs (635 and 73, respectively without and with toys), no formal conclusion could be drawn.

Newborns 0 to 6 months old

Exposure scenarios are the same for newborns and infants. The MOSs are calculated in two ways: with and without toys taking into account the whole internal exposures pathways for those specific consumers.

For repeated dose toxicity, the MOSs are considered sufficient to protect newborns, except for the scenario with toys, based on the repeated dose toxicity dog study. So, in case DIDP should be a substitute for other phthalates in toys in the future, the MOS of 33, derived from hepatic toxicity in dogs, would not be considered sufficient to protect newborns. Conclusion (iii). Pertaining to reduced offspring survival (trans-generational effect observed in a two- generation rat study), in any case, owing to the uncertainty on the applicability of the NOAEL (16.5 mg/kg bw/d in rats) and the significance of the MOSs (635 and 73, respectively without and with toys), no formal conclusion could be drawn.

Humans exposed via the environment

The exposure assessment has shown that the main route of intake is by the oral route.

For repeated dose toxicity, in adults and infants 3-15 years old, the MOSs have been calculated for the lowest NOAELs (the internal NOAEL for hepatic effects in rats being set at 30 mg/kg bw/d and the internal NOAEL for hepatic effects in dogs being set at 7.5 mg/kg bw/d). The estimated MOSs are considered sufficient for exposure of this population via the environment. In infants 0.5-3 years old, as the bioavailability of DIDP in children is assumed to be higher than in adults, an internal dose corresponding to 100% of the external dose will be used. The MOSs have been calculated for the lowest NOAELs (the internal NOAEL for hepatic effects in rats being set at 30 mg/kg bw/d and the internal NOAEL for hepatic effects in dogs being set at 7.5 mg/kg bw/d). The estimated MOSs are considered sufficient for exposure of infants via the environment. Conclusion (ii).

For fertility, in adults and children 3-15 years old, the estimated MOSs for offspring survival are considered sufficient for exposure of adults via the environment. Pertaining to reduced offspring survival (trans-generational effect observed in a two-generation rat study), in any case, owing to the uncertainty on the applicability of the NOAEL (16.5 mg/kg bw/d) and the significance of the MOS (93), no formal conclusion could be drawn.

For developmental toxicity, considering the relevant NOAELs of 500 mg/kg/d (skeletal variations) and 253 mg/kg/d (decrease in body weight), the MOSs can be calculated and are considered sufficient to protect adults. Conclusion (ii).

Combined exposure

As combined exposure of adults is almost exclusively related to occupational exposure, the MOSs are considered sufficient for adults. For children 3-15 years old, the MOSs are also considered sufficient. Conclusion (ii).

As combined infant exposure without toys is almost exclusively related to environmental exposure, the MOSs are considered to protect infants 0.5-3 years old. For repeated dose toxicity, the MOSs are considered sufficient to protect infants, except for the scenario with toys, based on the repeated dose toxicity dog study. So, in case DIDP should be a substitute for other phthalates in toys in the future, MOS of 18.8, derived from hepatic toxicity in dogs, would not be considered sufficient to protect infants. Conclusion (iii).

Pertaining to reduced offspring survival (trans-generational effect observed in a two- generation rat study), in any case, owing to the uncertainty on the applicability of the NOAEL (16.5 mg/kg bw/d) and the significance of the MOSs (83 and 41, respectively without and with toys), no formal conclusion could be drawn.

HUMAN HEALTH (PHYSICO-CHEMICAL PROPERTIES)

No specific exposure information is available on the exposure assessment for workers. Concerning the effect assessment, the properties of explosivity, flammability and oxidisation are not considered to pose a hazard. Conclusion (ii).

Source & ©: ECB "2003 Risk Assessment Report (RAR 041) on
Di-"isodecyl" Phthalate (DIDP), Summary of the Report, chapter 4: Human Health

DINP

Consumers

As DINP is present in several end products available to consumers, especially those in soft- PVC, consumer exposure can occur from various sources by different routes (inhalation, dermal, oral) in different situations. Scenarios were built for three subpopulations:

Adults and children 3-15 years old

The MOSs are calculated for multiple exposure pathways and include exposure from the four scenarios (Food and food-related uses / Building materials and furniture / Clothes, gloves and footwears / Car and public transport interior). For all endpoints, the MOSs are considered sufficient for adult consumers. Conclusion (ii).

Infants 6 months to 3 years old

Four exposure scenarios are considered as important for infants and newborns: Food and food-related uses / Toys and baby equipment / Car and public transport interior / Building material and furniture. The MOSs are calculated in two ways: with or without toys exposure. For all endpoints, the MOSs are considered sufficient for infants.

Pertaining to reduced offspring survival (observed in the one-generation rat study), in any case, owing to the uncertainty related to the relevance of this endpoint for infants, no formal conclusion could be drawn. Nevertheless, considering the NOAEL of 311 mg/kg bw/d, the MOSs (6,347 and 1,244, respectively without and with toys) would be sufficient to protect infants.

Conclusion (ii).

Newborns 0 to 6 months old

Exposure scenarios are the same for newborns and infants. The MOSs are calculated in two ways: with and without toys taking into account the whole internal exposure pathways for those specific consumers.

For all endpoints, the MOSs are considered sufficient for newborns.

Pertaining to reduced offspring survival (observed in the one-generation rat study), in any case, owing to the uncertainty related to the relevance of this endpoint for newborns, no formal conclusion could be drawn. Nevertheless, considering the NOAEL of 311 mg/kg bw/d, the MOSs (6,347 and 1,244, respectively without and with toys) would be sufficient to protect newborns.

Conclusion (ii).

Humans exposed via the environment

The exposure assessment has shown that the main route of intake is by the oral route.

For repeated dose toxicity, in adults and children 3-15 years old, the highest estimated total daily intake is 0.028 mg/kg bw/d, corresponding to an internal exposure of 0.014 mg/kg bw/d. The estimated MOS is considered sufficient for the exposure of this population via the environment. In infants (0.5-3 years old), the highest estimated total daily intake is 0.156 mg/kg bw/d, corresponding to an internal dose of 0.156 mg/kg bw/d. The estimated MOS is considered sufficient for the exposure of this sub-population via the environment, especially as the risk characterisation is specific for young children and not the overall population.

For reproductive toxicity, in adults and children 3-15 years old, the calculated MOSs for the lowest NOAELs determined for fertility and developmental effects, are considered sufficient for the exposure of this population via the environment. In infants (0.5-3 years old), a MOS of 885 was calculated for the lowest NOAELs determined for fertility (testicular effects). Moreover, reduced offspring survival, observed in the one-generation rat study, might be taken into account for infants and considering the internal exposure of 0.156 mg/kg bw/d and the internal NOAEL of 311 mg/kg bw/d in rats, the MOS would be 1,994. These MOSs are considered sufficient for the exposure of infants via the environment.

Conclusion (ii).

Combined exposure

As combined exposure of adults is almost exclusively related to occupational exposure, the MOSs indicate no reason for concern. For children 3-15 years, the MOSs also indicate no reason for concern. Conclusion (ii).

Pertaining to reduced offspring survival (observed in the one-generation rat study), owing to the uncertainty related to the relevance of this endpoint for infants, no formal conclusion could be drawn.

HUMAN HEALTH (PHYSICO-CHEMICAL PROPERTIES)

No specific exposure information is available on the exposure assessment for workers. Concerning the effect assessment, the properties of explosivity, flammability and oxidisation are not considered to pose a hazard. Conclusion (ii).

Source & ©: ECB "2003 Risk Assessment Report (RAR 046) on
Di-"isodecyl" Phthalate (DIDP), Summary of the Report, chapter 4: Human Health

For more information, see the full ECB Risk Assessment Report:
 Chapter 4: Human Health

The same information on