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Key value for chemical safety assessment

Effects on fertility

Description of key information
no study available
Effect on fertility: via oral route
Dose descriptor:
30 mg/kg bw/day
Effect on fertility: via inhalation route
Dose descriptor:
9 mg/m³
Additional information

Three studies are available describing the toxicity to reproduction of 1,2,3-trichloropropane. One oral 2 generation study and 2 inhalation one generation studies.

- Oral:

A reliable study for the oral route of exposure is available. In Gulati 1990 the reproductive toxicity of 1,2,3-trichloropropane was tested in a 2 generation study with unique test design (continuous breeding protocol) where CD-1 Swiss mice were treated via gavage with 0, 30, 60 and 120 mg/Kg bw in corn oil. In the parent generation adverse effects on the reproductive performance, on sex ratio, on pup weight and on reproductive organ weights were seen at 60 and 120 mg/Kg bw, at which slight signs of parental toxicity were noted (moderately raised liver and kidney weights). The effects on reproductive performance was both time and dose dependent. In the offspring these effects were confirmed but only for the 120 mg/Kg group, except for effects on estrus cyclicity that were seen down to 30 mg/Kg bw. The induced toxicity was regarded to slight to explain the marked adverse effects in both generations. The cross mating experiment (Task 3) failed to clearly identify the affected sex, though the data suggests a slightly greater reproductive toxicity for females.

Based on these results 1,2,3 -trichloropropane is deemed a reproductive toxicant. Due to the limited set of investigations, a clear NOAEL is difficult to derive. Following a conservative approach based on the effects on estrus cyclicity in the F1 generation a LOAEL of 30 mg/Kg bw is deduced.

This assessment is in-line with the evaluation of the Concise International Chemical Assessment Document 56 on 1,2,3-TRICHLOROPROPANE (International Program on Chemical Safety (IPCS) 2003,

- Dermal: no study available

- Inhalation:

Two 1-generation studies using inhalation exposure in the rat that were conducted successively (Monsanto 1980 and Johannsen 1988). In Johannsen no adverse effects were found for mating performance, fertility, pup viability or weight development up to a level of 1.5 ppm (= 9.0 mg/m³, 5 d/wk during 10 wks premating + 5d/wk during 30 d of mating + d 0 - d 14 of gestation). From Monsanto 1980 (0,5,15 ppm = 0,30, 90 mg/m³; 5 d/wk 10 wks premating + mating + d 0 - d 14 of gestation) due to the low overall mating performance of treated as well as control males no clear statement can be made. Pup viability and weight development showed no significant difference up to a treatment concentration of 15 ppm. These two studies are not fully reliable due to several deficiencies: no dosing throughout gestation and during the lactation, mating success too low to assess subtle effects, only limited histological examination of reproductive organs and other tissues. Therefore a clear NOAEC for toxicity of reproduction cannot be deduced.

Short description of key information:
- Oral: LOAEL: 30 mg/Kg bw for the rat, 2-generation study with unique study design by NTP; Gulati (1990) (1976)
- Dermal: no study available
- Inhalation: NOAEC: 9 mg/m³ for the rat, 1-generation study comparable to OECD TG 415, but not fully reliable; Johannsen (1988)

Effects on developmental toxicity

Description of key information
- Oral:           no study available
- Dermal: no study available
- Inhalation: no study available
- Other: intraperitoneal injection, NOAEL = 37 mg/Kg bw for the rat, generally compliant to OECD TG 414, but not reliable; study Hardin (1981)
Additional information

- Oral: no study available

- Dermal: no study available

- Inhalation: no study available

- Intraperitoneal injection:

Only one study is available where 1,2,3-trichloropropane was tested for developmental toxicity in a general compliance to OECD 414. Pregnant Sprague Dawley rats were treated with a previously determined MTD of 37 mg/Kg bw from gestation day 1 to 15 via i.p. injection. At gestation day 21 they were sacrificed and a full teratology examination was performed.

Maternal toxicity was found at the only tested dose but no signs of fetal toxicity or teratogenicity. Therefore a NOAEL of 37 mg/Kg bw can be derived for developmental toxicity, though the reliability of the study is limited due to the design of the study a screening test (only one dose was tested and as individual animal data and methodological details are not reported). But since neither in this study nor in the 2 generation study (Gulati 1990) or the 1 generation studies (Monsanto 1980 and Johannsen 1988) fetotoxic or teratogenic effects were observed a hypothetical, undisclosed developmental toxicity of 1,2,3-trichloropropane is unlikely.

Toxicity to reproduction: other studies

Additional information

no study available

Justification for classification or non-classification

- Effects on fertility:

Based on the above stated results 1,2,3-trichloropropane is deemed a presumed human reproductive toxicant Categorie 1B (Danger: H360: May damage fertility or the unborn child) to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

- Effects on developmental toxicity/teratogenicity:

Based on the above stated results 1,2,3-trichloropropane cannot be clearly classified for developmental toxicity according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

As the substance is classified and labelled as a reproductive toxicant a hypothetical hazard stemming from a so far uncovered developmental toxicity is sufficiently covered by the existing classification and labelling.

As the substance is known to be a potentially genotoxic carcinogen the corresponding risk implemented management measures are surely sufficient to cover a potential risk from this hypothetical developmental toxicity.