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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

In relation to fertility, there is no relevant information currently available in humans and there are no laboratory animal studies specifically investigating such effects. A two-generation study is proposed. However, effects on the reproductive organs have been assessed in repeated dose toxicity studies.

In a 14-day toxicity study (to GLP, and similar to OECD Guideline 407), groups of 5 male and 5 female Fischer 344 rats were given a C10-12 chlorinated paraffin (58% chlorinated) by oral gavage (in corn oil) at doses of 0, 30, 100, 300, 1000 and 3000 mg/kg bw/day (see IUCLID Chapter 7.5.1 for further details). In top dose animals, a statistically significant decrease in absolute and relative ovary weights (35 to 48%, respectively) was seen compared to controls, and a slight decrease in testis weights, whereas no changes were seen in the ovaries or testes at 1000 mg/kg bw/day and below. Other signs of toxicity, including a 20% decrease in body weight gain, were also noted in the top dose animals and the effect on the ovaries is likely to be secondary to this. No dose response was seen, and no changes in the ovaries were seen at 1000 mg/kg bw/day. Therefore, a no-observed-effect level (NOEL) in this study was considered to be 1000 mg/kg bw/day, based on effects on thymus and ovaries weights at the top dose level (IRDC, 1981).

In a 14-day toxicity study (to GLP, and similar to OECD Guideline 407), groups of 5 male and 5 female Fischer 344 rats were given a C10-12 chlorinated paraffin (58% chlorinated) in the diet at doses of 0, 30, 100, 300, 1000 and 3000 mg/kg bw/day (see IUCLID Chapter 7.5.1 for further details). Top dose males showed reduction in the size of the tubules and therefore the organ as such. No degeneration or maturation arrest was evident. Normal spermatogonia, spermatids and spermatazoa were present indicating that the change was hypoplastic in nature (IRDC, 1983). Atrophy of the testes in top dose animals was considered to be secondary to reduced food consumption.

No changes were seen (in good quality NTP studies, to GLP) in the seminal vesicles, prostate, testes, ovaries or uterus of rats and mice administered a C12 chlorinated paraffin (60% chlorination) at up to 5000 and 2000 mg/kg bw/day, respectively, for 13 weeks (NTP, 1986; see IUCLID Chapter 7.5.1 for more details).

Overall, therefore, a conservative NOAEL of 1000 mg/kg bw/day will be used for the risk characterisation.


Short description of key information:
In relation to fertility, there is no information available in humans and there are no laboratory animal studies specifically investigating such effects. In a GLP study (IRDC, 1981), male and female rats were administered a C10-12 chlorinated paraffin (58% chlorination) by oral gavage for 14 days at doses of 0, 30, 100, 300, 1000 or 3000 mg/kg bw/day and all surviving animals were killed and a complete post-mortem and tissue examination was performed. In top dose animals, a statistically significant decrease in absolute and relative ovary weights (35 to 48%, respectively) was seen compared to controls, and a slight decrease in testis weights, whereas no changes were seen in the ovaries or testes at 1000 mg/kg bw/day and below. . However, no changes were seen in the reproductive organs in rats and mice treated with a C12 chlorinated paraffin (60% chlorination) for 13 weeks with up to 5000 and 2000 mg/kg bw/day, respectively (NTP, 1986).

Effects on developmental toxicity

Description of key information
In terms of developmental effects, there is no information currently available in humans. In a well-conducted study in rats a C10-13 chlorinated paraffin (58% chlorination) produced developmental effects at a dose which also caused severe maternal toxicity (2000 mg/kg bw/day), but no developmental effects were seen at lower doses (500 mg/kg bw/day and below) (IRDC, 1982). No developmental effects were observed in a study in rabbits at up to 100 mg/kg bw/day, although maternally toxic doses were not tested (Miller, 1983). 
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
500 mg/kg bw/day
Additional information

In a well conducted GLP study, similar to OECD Guideline 414, groups of 25 mated female COBS CD rats were given 0, 100, 500 or 2000 mg/kg bw/day of a C10 -12 chlorinated paraffin (58% chlorination) in corn oil by oral gavage on days 6 to 19 of gestation. Animal were killed on day 20 and the numbers and location of viable and non-viable foetuses, resorption sites and the total number of implantations and corpera lutea were determined. Appearance and body weight gain of dams was monitored and all foetuses were examined for external malformations. Approximately one half of the foetuses from each litter were examined for visceral malformations and the other half for skeletal abnormalities. Clinical signs of maternal toxicity were seen in both 500 and 2000 mg/kg bw/day groups, comprising yellow or brown matting and staining of the coat in the anogenital region, red or brown staining in the nasal region, excessive salivation, lethary and emaciation. The effects were at an increased frequency in the top dose animals. A decrease in body weight gain from days 9 to 16 and 8/25 pregnant rats died between gestation days 16 and 20 in the top dose group. Significant increases in the numbers of post-implantation losses, due to both early and late resorptions, and a decrease in the numbers of viable foetuses was seen in the top dose group only. Foetal malformations (adactyly and/or shortened digits) were seen in 19 foetuses from 3/15 litters examined from the top dose animals. Overall, no developmental toxicity was seen in animals in the 500 mg/kg bw/day group, and no adverse effects were seen in dams or foetuses in the control or 100 mg/kg bw/day groups. Therefore, the no-observed-adverse-effect level (NOAEL) for developmental toxicity in the rat in this study was 500 mg/kg bw/day (Spicer et al. 1982).

In a GLP study, similar to OECD Guideline 414, groups of 16 mated female Dutch belted rabbits were given 0, 10, 30 or 100 mg/kg bw/day of a C10 -13 chlorinated paraffin (58% chlorination) in corn oil by oral gavage on days 6 to 27 of gestation. Animals were killed on day 28 and the numbers and location of viable and non-viable foetuses, resorption sites and the total number of implantations and corpera lutea were determined. Appearance and body weight gain of dams was monitored and all foetuses were examined for external malformations. Approximately one half of the foetuses from each litter were examined for visceral malformations and the other half for skeletal abnormalities. No maternal deaths occurred and no signs of toxicity were seen in any of the groups. Whole litter resorption was seen in two dams from the top dose group and one from the mid dose group and a slight increase in mean post-implantation loss was also seen in this group. However, all of these signs of embryotoxicity were within historical control levels and are not considered to provide evidence for a treatment-related effect. Therefore, the NOAEL for developmental and maternal toxicity in this study is 100 mg/kg bw/day (the highest tested dose) (Miller, 1983).

Overall, therefore, a NOAEL of 500 mg/kg bw/day for developmental effects will be used for the risk characterisation.

Justification for classification or non-classification

There are no reproductive toxicity studies in laboratory animals, although a testing proposal for a 2-gen study has been included in this REACH dossier. Effects on the reproductive organs have been assessed in repeated dose toxicity studies in laboratory animals. No changes were seen in the reproductive organs of rats and mice treated with a C12 chlorinated paraffin (60% chlorination) for 13 weeks with up to 5000 and 2000 mg/kg bw/day, respectively (NTP, 1986). In reliable studies, no developmental effects were seen when rats and rabbits were repeatedly dosed with SCCP during pregnancy at up to 500 and 100 mg/kg bw/day, respectively.

Therefore, SCCPs do not meet the classification requirement for developmental or reproductive toxicants under EU DSD or CLP regulations.