Hydrocarbons, C5, ethylene-manuf.-by-product, hydrogenated

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

There are no additional studies of relevance in relation to toxicity to reproduction

Additional information

Although no full multigeneration studies exist for this stream category, there are screening assessment data for two C5 non-cyclics streams, Pyrolysis C5 (CAS No 68476 -55 -1) and Hydrotreated C5 (CAS No 68602 -79 -9), and also on one major component 1, 3 pentadiene. Specific marker substances (isoprene, benzene, toluene and 1,3 -butadiene) and other potential components do not reveal significant reproductive toxicity at any exposure or dose level tested and are not classified under Annex I of the DSD. N-hexane (Classification: DSD Harmful, Xn R62; CLP- Category 2, H361r) causes specific adverse effects on testes, but the maximum level in C5 non-cyclics streams is 0.5% which is below the level that would trigger classification.

Reproductive/developmental toxicity screening studies have been conducted on two C5 non-cyclics category streams. In both studies (HLS, 2004a & b), groups of 12 male and female rats were exposed for a 2-week pre-mating period and throughout mating. Females were then exposed until Day 19 of gestation, allowed to litter and rear their offspring to Day 4 of lactation. Animals were exposed by whole body inhalation exposure for 6 h/day for 7 days/week. In the study with Pyrolysis C5 (HLS, 2004a), at exposure concentrations of 0, 100, 300 or 1000 ppm, there were no effects on reproduction with the no effect level being 1000 ppm. In the study with Hydrotreated C5 (HLS, 2004b) with exposure concentrations of 0, 1000, 3000 and 8500 ppm there was no evidence of reproductive toxicity at the highest concentration tested of 8500 ppm (analysed concentration 8502 ppm).

In the reproductive/developmental toxicity screening study with 1,3-pentadiene in which doses of 0, 30, 100, 1000 mg/kg day were administered by oral gavage (EBSI, 1992a), there were no effects on reproductive parameters at the highest dose level tested, which is the limit dose for studies of this type.

Short description of key information:
It is recognised that there is a data gap for a multi-generation study (REACH reference 8.7.3). The applicant submits that this study does not need to be conducted as the C5 non-cyclics category streams contain at least 1% isoprene, which is classified as a Cat 3 mutagen and a Cat 2 carcinogen under DSD and appropriate risk management measures are implemented (handled in controlled conditions).
Data from reproduction screening studies on two streams within this category and a third with 1, 3 pentadiene do not indicate a need for classification. Of the specific component substances present in the C5 non-cyclics category streams, only n-hexane is considered to be a reproductive toxicant; but the maximum levels of n-hexane in C5 non-cyclics streams are below those which would warrant classification.

Effects on developmental toxicity

Description of key information

Based on reported findings, the C5 Non-cyclics Category streams are considered as having minimal potential to produce developmental effects.  For the specific component toluene (present in some streams at a maximum of 4%) there is some evidence of developmental toxicity (lower body weight at birth and delayed vaginal opening) at exposure concentrations ≥ 1000 ppm, concentrations which are associated with slight maternal toxicity. The NOAEC for developmental and maternal effects is 600 ppm (2261 mg/m3).

Additional information

Although no developmental toxicity studies exist for this stream category, there are screening assessment data for two C5 non-cyclics category streams, Pyrolysis C5 (CAS No 68476-55-1) and Hydrotreated C5 (CAS No 68602 -79 -9), and also on one major component, 1,3 pentadiene.

For Pyrolysis C5 and Hydrotreated C5 streams, the OECD TG 422 combined repeated dose and reproduction/developmental toxicity studies have been conducted in Sprague Dawley rats (HLS, 2004 a & b). In both studies there were no evidence of developmental toxicity. In conclusion, the NOAELs for developmental toxicity in these screening studies were 1,000 ppm and 8502 ppm respectively.

An OECD TG 422 combined repeated dose and reproduction/developmental toxicity study was conducted in Sprague Dawley rats (oral dosing) was conducted on 1,3 -pentadiene (EBSI, 1992a). The NOAEL for developmental toxicity in this screening study was 1000 mg/kg bw/d, the maximum dose tested.

Specific marker substances (isoprene, benzene and 1,3-butadiene) and other potential components do not reveal significant developmental toxicity at an exposure or dose level tested and are not classified under Annex I of the DSD.

Toluene (Classification: DSD – Harmful Xn, R63; CLP – Category 2, H361d): There is no evidence that toluene produces malformation in animals or humans. There is some evidence of developmental toxicity (lower body weight at birth and delayed vaginal opening) at toluene exposure concentrations ≥ 1000 ppm, concentrations which are associated with slight maternal toxicity. The NOAEC for developmental and maternal effects is 600 ppm (2261 mg/m³) (Thiel and Chahoud, 1997).

Justification for classification or non-classification

Based on both data for the streams and the individual components, no classification for reproductive toxicity is warranted.

In relation to developmental toxicity, data on the streams and individual components indicate that classification (Category 2, H361d) is only warranted under CLP where toluene is present at >=3%. Since toluene is present at <5%, no classification under DPD is warranted. If data on a C5 non-cyclics stream indicates a concentration of toluene between >=3% and <5% a classification as Category 2, H361d is warranted.