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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproduction Toxicity

READ ACROSS DATA: C16-C30 highly purified light mineral oil (60% paraffins, 40% naphthenes)

1-generation reproductive/developmental Test (OECD TG 415) - Dermal administration in females.

NOAEL for fertility, maternal toxicity and developmental toxicity 2000 mg/kg bw/day (highest dose tested)

READ ACROSS DATA: C16-C30 highly purified light mineral oil (60% paraffins, 40% naphthenes)

1-generation reproductive/developmental Test (OECD TG 415) - Dermal administration in males; 13-weeks prior to mating.

NOAEL for male fertility (sperm count, sperm morphology and spermatogenesis) for mineral oil 2000 mg/kg bw/day (highest dose tested)

READ ACROSS DATA: C13-C22 hydrocarbon fuel (30% n- & 70% iso-paraffins)

2-generation reproductive/developmental Test (OECD TG 416) - Oral administration in males and females.

NOAEL for fertility and developmental toxicity 750 mg/kg bw/day

READ ACROSS DATA: C9 aromatic naphtha

3-generation reproductive/developmental Test (OECD TG 416) - Inhalation

NOAEC (parental fertility; male/female) 1500 ppm

NOAEC for F1 offspring = 500 ppm (reduced body weights). LOAEC for F2 offspring = 100 ppm (reduced body weights)

READ ACROSS DATA: n-butylbenzene

2-generation reproductive/developmental Test (OECD TG 416) - Oral gavage

NOAEL (parental fertility; male/female) ≥300 mg/kg bw/day

NOAEL F1 and F2 offspring = 100 mg/kg bw/day (increased thymus weights)    

SUPPORTING DATA:  JP-8 Fuel (C9-C16 Aliphatics, 25% aromatics)

One-Generation Reproduction Toxicity Study (OECD TG 415) - Male Fertility Test – Oral Administration - 90d prior to mating, the NOAEL >=3000 mg/kg/day, which was the highest dose tested.

Female fertility NOAEL 1500 mg/kg (highest dose tested). Developmental NOAEL = 750 mg/kg (decreased BW)

Additional information

READ ACROSS DATA: C14-C20 aliphatics (<2% aromatic)

A reproductive/pre-natal developmental one-generational study was conducted to evaluate the reproductive performance (gonadal function, all 4 stages of the estrus cycle, fertilization, implantation of the egg, gestation period and parturition) of a C16-C30 highly purified light mineral oil (60% paraffins, 40% naphthenes). The pre-natal developmental phase also evaluated pup growth and development up to weaning. Female Sprague-Dawley rats were dermally exposed to test material for 10 weeks premating period (5 days/week), a 3-week mating period (5 days/week) and up to gestation day 20. Test material was applied once daily to clipped, intact dorsal skin at a dose level of 125, 500, 2000 mg/kg bw/day. No clinical signs of systemic toxicity were observed and there were no effects on maternal body weight and food consumption. No differences were observed in mean numbers of implantation sites, live pups/litter, live birth index (total pups born alive/total pups born) either at birth, or on days 4 or 21 postpartum. There was no change in mean pup body weights and no pathological observations were seen in necropsied organs of the pups. NOAEL for mineral oil was ≥ 2000 mg/kg bw/day for fertility and pre-natal development.

In males exposed to the same test substance for 13 weeks prior to mating, the reproductive performance was evaluated with regard to fertility, sperm count, sperm morphology and spermatogenesis. No changes in male reproductive organ weights or performance were observed. NOAEL for fertility was ≥ 2000 mg/kg bw/day.

READ ACROSS DATA: C13-C22 aliphatics (<2% aromatic)

F0 and F1 male and female rats were administered an oral gavage dose (50, 200 or 750 mg/kg bw/day) of a C13-C22 hydrocarbon fuel comprised primarily of aliphatic constituents (30% n- and 70% iso-paraffins) 5 days/week for at least 70 days premating and 14 days mating (for males). Test substance had no effect on reproductive performance (fertility), gestation length and parturition in both F0 and F1 rats. There were no test-related effects on postnatal survival, mortality, systemic toxicity, anogenital distance and pup weights in F1 and F2 litters. , NOAEL for fertility was greater than 750 mg/kg bw for males and females.

READ ACROSS DATA: n-Butylbenzene

N-butylbenzene, a C10 aromatic hydrocarbon, was examined for toxicity in a two-generation reproductive toxicity study. N-butylbenzene was administered by oral gavage at dose levels of 0, 30, 100, and 300 mg/kg/day to male and female rats over 2 generations. n- butylbenzene did not induce reproductive toxicity in the F1 parental animals and no effects on the endocrine system were observed. Therefore, the NOAEL was determined to be 300 mg/kg bw/day.

READ ACROSS DATA: C9 aromatic naphtha

A three generation reproductive toxicity test has been conducted on a complex C9 aromatic substance and no evidence of reproductive toxicity was found. F0 rats were exposed for 10 weeks prior and 2 weeks during mating to 0, 100, 500 or 1500 ppm (0, 505, 2430 or 7265 mg/m3) inhalation exposure for 6 hours/day, 5 days/week. Females were additionally exposed on gestation days 0-15 and lactation days 5-21. Exposures were continued through breeding of the F1 generation. No effects were reported on sperm morphology, gestational period, number of implantation sites, or post-implantation loss in any generation. The F2 generation exhibited a LOAEC of 103 ppm (505 mg/m3) based on reduced body weight and survival, while F0 and F1 generations had NOAECs of 495 ppm (2430 mg/m3) for these effects. Effects on Pups: A decrease was observed in F1 mid-dose body weights and F1 and F2 survival (F2: too few to evaluate for body weight due to poor survival in dams). No adverse developmental effects were reported in any generation at any exposure level. The reproductive NOAEC was 1480 ppm (7265 mg/m3), highest concentration tested.

SUPPORTING DATA: JP-8 Fuel (C9-C16 Aliphatics, 25% Aromatics) 

There were several studies located for the structurally analogous test material, JP-8 fuel. JP-8 fuel was examined for reproductive toxicity in a 70 day male and in a 90 day female one generation reproductive toxicity study (OECD TG 414). For the male reproductive toxicity study, the reproductive NOAEL >= 3000 mg/kg/day for male rats, which was the highest dose tested. For the female reproductive toxicity study, the reproductive NOAEL ≥1500 mg/kg/day for female rats, which was the highest dose tested. The F1 (fetus) NOAEL = 750 mg/kg/day based on a decrease in body weight that correlated to a decrease in maternal body weight.

Effects on developmental toxicity

Description of key information

OECD Guideline 414 (Prenatal Developmental Toxicity Study) - C15-C18+ aliphatics; < 2% aromatics - Oral Administration - The NOAEL for developmental toxicity was 1000 mg/kg/day and the NOAEL for teratogenicity was 1000 mg/kg/day, which was the highest dose tested.  

OECD Guideline 414 (Prenatal Developmental Toxicity Study) - Dermal, oral and inhalation in C16-C30 light mineral oil. NOAEL for developmental toxicity and NOAEL for teratogenicity was ≥ 2000 mg/kg bw/day (dermal), 1000 mg/m3 (inhalation) and 5000 mg/kg bw/day (oral gavage)

OECD Guideline 414 (Prenatal Developmental Toxicity Study) - C9 aromatic naphtha. Both maternal and fetal NOAELs ranged from 100 to 300 ppm (500 – 1500 mg/m3). Fetotoxic effects seen at doses that correlate with severe maternal toxicity and death.

OECD Guideline 414 (Prenatal Developmental Toxicity Study) - C10-C12 aromatic solvent. Maternal NOAEL was 150 mg/kg bw/day on the basis of significantly reduced maternal body weight gain and food consumption. Developmental NOAEL was ≥ 450 mg/kg bw/day (highest dose tested)

OECD Guideline 414 (Prenatal Developmental Toxicity Study) - C24 alkylated naphthalene. No developmental effects were observed and NOAEL was ≥ 1000 mg/kg bw/day, the highest dose tested.

Additional information

READ ACROSS DATA: C15 to C18+ n-alkanes, iso-alkanes, cyclies; <2% aromatics

In a pre-natal development study, no developmental effects were noted following oral exposure to a mixed aliphatic solvent (C15-C18+; < 2% aromatics). NOAEL was ≥ 1000 mg/kg bw/day (highest dose tested)

READ ACROSS DATA: C16 to C30 highly purified light mineral oil (60% paraffins, 40% naphthenes)

A series of studies were conducted to evaluate the teratogenic effects of a C16-C30 light mineral oil in pregnant Sprague-Dawley rats by three separate routes of exposure; inhalation (1000 mg/m3), dermal (2000 mg/kg bw/day), oral gavage (5000 mg/kg bw/day) with exposures on gestation days 6-19. Due to low vapor pressure, the mineral oil was delivered as an aerosol for the inhalation study though aerosol particle size generated was well within the respirable range. There were no observable maternal effects (food consumption, body weight gain) irrespective of route of exposure. No adverse effects on reproductive parameters (implantation number, resorptions, fetal viability) or fetal parameters (body weight, crown-rump length) were observed in any of the studies. There was a clear lack of teratogenicity with regard to abnormal ossification, and adverse effects to external or soft tissue. Spontaneous anomalies were noted in some exposure groups but were not considered exposure related since incidence of such occurrences were similar in the sham-exposed groups. NOAEL for developmental toxicity was ≥ 2000 mg/kg bw/day (dermal), 1000 mg/m3 (inhalation) and 5000 mg/kg bw/day (oral gavage).

READ ACROSS DATA: C9 aromatic naphtha

The developmental toxicity of a C9 aromatic naphtha (mostly ethyl and trimethyl-benzenes) was evaluated in mice exposed to 0, 100, 500 and 1500 ppm from gestation days 6 -15. Delayed sternebral and cranial ossifications along with an increased incidence of cleft palate was noted. However, these effects were seen at the highest concentration tested (1500 ppm) which was associated with severe maternal toxicity (44% mortality), an indication that these defects are a result of maternal toxicity and not related to specific developmental toxicity of C9 aromatic naphtha. Both maternal and fetal NOAECs ranged from 100 to 300 ppm (500 – 1500 mg/m3)

READ ACROSS DATA: C24 alkylated naphtha

A pre-natal developmental toxicity study was conducted to evaluate the fetal developmental effects of C24 alkylated naphthalene administered by oral gavage. No developmental effects were observed and NOAEL was ≥ 1000 mg/kg bw/day, the highest dose tested

READ ACROSS DATA: C10 -C12 aromatic solvent

A pre-natal developmental study in pregnant rats exposed to 0, 75, 150 or 450 mg/kg bw/day of a C10-C12 aromatic solvent (predominant aromatic constituent range in Category 4 [C16 -C20 aliphatics; 2 -30% aromatics] solvents) by oral gavage did not show any significant increase in fetal toxicity. Maternal NOAEL was 150 mg/kg bw/day on the basis of significantly reduced maternal body weight gain and food consumption. Developmental NOAEL was ≥ 450 mg/kg bw/day

Justification for classification or non-classification

These findings do not warrant classification of C14-C20 aliphatic, 2-30% aromatics as a reproductive or developmental toxin under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.