Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

This endpoint is not a REACH requirement.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available (further information necessary)
Additional information

No guideline or near-guideline studies were located that have examined the potential impact of straight-run gas oils on reproductive function.Some indication of the likely effect of a test substance on reproductive organs can be gained from the results of repeated-dose toxicity studies with members of this category, which did not show any treatment related effects on reproductive organs or sperm parameters (See Table). Nevertheless, a testing proposal for an extended one-generation study with a representative sample for the category is included.

Table. Summaries of data on reproductive organs from subchronic studies with SRGO. 

(Robust study summaries are provided in Section 7.5 Repeated Dose Toxicity)

Test Material

Route, Species, Doses, Exposure Regimen

Endpoints

Results

Reference

Straight run middle distillate (API 83-11)

Dermal. Rabbit.

0, 200, 1000, 2000 mg/kg, applied to skin, covered with gauze pad, and wrapped for 6 hr, 3 d/wk for 4 wk.

Weights of ovaries and testes. Histopathology of ovaries and testes at 2000 mg/kg.

No treatment-related effect on reproductive organs noted.

API, 1985

Intermediate gas oil (F-130)

Dermal. Rat.

0, 0.01, 0.10, 0.50 ml/kg, applied to skin, covered with gauze pad and wrapped for 6 hr, 5d/wk for 4 wk.

Weights of ovaries and testes. Histopathology of ovaries and testes at 0.50 ml/kg.

No treatment-related effect on reproductive organs noted.

ARCO, 1992

Short description of key information:

Study proposal to fulfill the information requirements of REACH Annex IX (8.7.3). In a number of repeat dose (dermal) and several OECD 414 developmental toxicity studies there were no effects observed on development. In addition, no effects were observed on reproductive organs in subchronic studies with SRGO and an assessment of the overall weight of evidence (as outlined in the attached testing proposal) concludes that it is unlikely that the primarily aliphatic SRGOs have an adverse effect on fertility.

Effects on developmental toxicity

Description of key information

A key dermal developmental study (OECD 414) was identified.  The study authors reported a NOAEL of 50 mg/kg body weight/day based on based significant decrease in pup body weight and increase in external, visceral, and skeletal malformation following repeated dermal application of straight-run petroleum gas oil (F-193). The maternal LOAEL was 50 mg/kg/day, based on dermal effects. 

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Species:
rat
Additional information

In a key developmental study, the developmental NOAEL was 50 mg/kg bw/day, based on significant decrease in pup body weight and increase in external, visceral, and skeletal malformation following repeated dermal application of straight-run petroleum gas oil (F-193).

In a key developmental toxicity study (ARCO, 1993a), straight-run petroleum gas oil (F-193) in acetone was dermally administered to 25 presumed pregnant rats/dose at dose levels of 0, 50, 250, or 500 mg/kg bw/day from days 0 through 19 of gestation.

 

Skin reactions (erythmea, oedema, atonia, and desquamation) occurred in all treatment groups. There was a significant reduction in body weight and feed consumption in the 250 - and 500 -mg/kg/day groups.  There was also a significant reduction in average litter size and live foetuses, increased resorptions in these groups. The maternal LOAEL was 50 mg/kg/day, based on dermal effects. There was no maternal NOAEL. 

There was a significant decrease in pup body weight and increase in external, visceral, and skeletal malformations in the mid- and high-dose groups.The developmental LOAEL was 250 mg/kg/day, based on pup body weight and malformations. The developmental NOAEL was 50 mg/kg/day.

 

In a supporting developmental toxicity study, gas oil intermediate was dermally administered to 12 to 15 Sprague-Dawley rats/dose at dose levels of 0, 50, 150, or 500 mg/kg bw/day from days 0 through 20 of gestation (ARCO 1994b). There was a significant reduction in maternal body weight and body weight gain in the high-dose group. Dermal irritation occurred in all dose groups. There were no treatment-related effects in survival, clinical signs, or caesarean parameters. The maternal LOAEL was 50 mg/kg/day, based on dermal irritation. The maternal NOAEL was > 50 mg/kg/day. Pup body weight was significantly reduced at lactation days 0 and 4 in the mid- and high-dose group. In the high-dose group, there was a decrease in pup survival on lactation day 4. There were no treatment-related effects noted in external abnormalities. The developmental LOAEL was 150 mg/kg/day, based on reduced pup weight. The developmental NOAEL was 50 mg/kg/day.

 

In an additional supporting developmental toxicity sty, straight-run petroleum gas oil (F-215) in acetone was dermally administered to 25 presumed pregnant rats/dose at dose levels of 0, 50, 250, or 500 mg/kg bw/day from days 0 through 19 of gestation (ARCO, 1993b).  Skin reactions occurred in the mid- and high-dose groups with vocalization occurring in eight of the high-dose animals. There was a significant reduction in body weight and body weight gain in the 250 - and 500 -mg/kg/day groups, but food consumption was only affected in the high-dose group. There were no biologically significant changes in any reproduction or developmental parameters. The maternal LOAEL was 250 mg/kg/day, based on dermal effects and body weight/body weight gain. The maternal NOAEL was 50 mg/kg/day. There was no developmental LOAEL, based on the lack of effects at the high dose. The developmental NOAEL was greater than or equal to 500 mg/kg/day.

 

Additional data support that straight run gas oils are not developmental toxicants (UBTL, 1994). This information is presented in the dossier.

Justification for selection of Effect on developmental toxicity: via dermal route:

One of 3 dermal developmental toxicity studies on straight run gas oils. Foetal effects only observed in the presence of maternal toxicity (reduced body weight and food consumption effects and dermal irritation)

Toxicity to reproduction: other studies

Additional information

This endpoint is not a REACH requirement.

Justification for classification or non-classification

No extended one-generation reproductive toxicity data are available for Straight-Run Gas Oils. Therefore, there are insufficient data to classify Straight-Run Gas Oils as toxic for reproduction under the EU CLP Regulation (EC No. 1272/2008).

However, in a screening study there were no effects on female reproductive capacity. In addition, no effects were observed on reproductive organs or sperm parameters in repeat dose toxicity studies with SRGO and related materials. An assessment of the overall weight of evidence (as outlined in the attached testing proposal hypothesis) concludes that it is unlikely that the primarily aliphatic SRGOs have an adverse effect on fertility. Nonetheless, to fulfil the information requirements of REACH Annex IX (8.7.3) a testing proposal for an extended one-generation reproductive study has been submitted.

In a key dermal developmental study with a straight run gas oil a foetal NOAEL of 50 mg/kg/day was determined. The LOEL for maternal toxicity was 50mg/kg, based on reduced body weight and food consumption effects and dermal irritation. No classification for effects on development is proposed however since it is not possible to separate out the ‘indirect’ effects of maternal toxicity from any direct effects on the foetus, which is supported by additional supporting studies for this endpoint.

Additional information