4-chloro-α,α,α-trifluorotoluene

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive toxicant after a sub-chronic inhalation exposure (LOAEC = 125 ppm for males mice based on a decreased sperm motility)

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

45 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

There is only one study but it is of high quality (GLP, data reporting complete and accurate)

Effect on fertility: via inhalation route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEC

125 ppm

Study duration:

subchronic

Experimental exposure time per week (hours/week):

30

Species:

mouse

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A one generation study was carried out on rats administered by oral gavage. The procedure followed was similar to the OECD guideline 415.

170 Sprague-Dawley rats were used to test the subchronic toxicity of PCBTF in F1 rats following in utero exposure. Rats were divided randomly into 4 treatment groups: Group I (control), Group II (5 mg/kg/day), Group III (15 mg/kg/day), Group IV ( 45 mg/kg/day). Rats were dosed in 2 mL/kg body weight volumes via gavage with test solutions of varying concentrations for each dosage. Test material was administered to the parental (F0) rats for 76 to 83 days. F0 rats were killed and subjected to a gross necropsy. Weanling F1 rats were dosed for at least 90 days, then killed and necropsied.

Throughout the study, weekly feed consumption and body weights were recorded; new doses were calculated weekly on the basis of current body weights. Clinical pathology parameters were obtained predose on baseline animals, after 14 days treatment of F0 rats, and terminally on F1 animals, and selected organ weights were recorded. Organ/body weight ratios were calculated. Statistical aualysis were perfomed on all tested measurable parameters. Clinical observations, clinical pathology parameters, and histopathology examinations showed no treatment related abnormalities.

A trend was observed in main liver weights and mean liver/body weight ratios among treatment groups. The effects seen were a physiologic response of this organ to PCBTF. The increased metabolic response did not reflect necessarily a toxic response to the test material. No other treatment related effects were observed. Under the conditions of the test, the test item PCBTF was found to be safe at all levels. A toxic no-effect level in rats was greater than or equal to 45 mg/kg.

 

Data on the functionality of the organs involved in the reproductive performance are also available from two subchronic studies on rats and mice (NTP TR 594, 2018).

PCBTF was administered at 0, 125, 250, 500, 1,000, or 2,000 ppm for 6 hours plus T90 (15 minutes) per day, 5 days per week for 14 weeks. 

Males rats exposed to 2,000 ppm had significantly decreased left cauda and left epididymis weights and numbers of sperm per cauda epididymis. Sperm motility was also significantly decreased in 1,000 and 2,000 ppm males. These findings were associated with histopathologic changes in the testes and epididymides. Female rats exposed to 2,000 ppm had decreased frequency of estrus and increased frequency of diestrus, a significantly higher probability of extended diestrus, a fewer number of cycles, and a fewer number of rats exhibiting cycles. 

All exposed groups of males mice evaluated displayed significant exposure concentration-related decreases in sperm motility. In 1,000 and 2,000 ppm females, there were significant increases in estrous cycle length. In all exposed female mice groups evaluated, there were significantly higher probabilities of extended estrus. 

Effects on developmental toxicity

Description of key information

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 study available

Justification for classification or non-classification

According to the CLP Regulation n.1272/2008, substances are allocate in Category 2 "suspected human reproductive toxicant", when the following criteria are met:

- there is some evidence from humans or experimental animals, possibly supplemented with other information, of an adverse effect on sexual function and fertility, or on development, and where the evidence is not sufficiently convincing to place the substance in Category 1. If deficiencies in the study make the
quality of evidence less convincing, Category 2 could be the more appropriate
classification.
Such effects shall have been observed in the absence of other toxic effects,
or if occurring together with other toxic effects the adverse effect on
reproduction is considered not to be a secondary non-specific consequence of
the other toxic effects.

Data on the two subchronic studies on rats and mice, show adverse effects on the sexual functions of both species. In particular, sperm motility is the most affected parameter. No studies on other species have been carried out and no human data is available. 

For this reason, the test substance is classified as reproductive toxicant category 2 according to the CLP Regulation n. 1272/2008.