4-chloro-α,α,α-trifluorotoluene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Inhalation toxicity, neurotoxicity, and toxicokinetic studies of p-chlorobenzotrifluoride

Author:

Newton, P.E., Bolte, H.F., Richter, W.R., Akinsanya, M.B., Knaak, J.B., and Smith, L.W

Year:

1998

Bibliographic source:

Inhal Toxicol, 10(1):33-48

Materials and methods

Principles of method if other than guideline:

10 animals/sex/group were exposed via whole-body inhalation exposure for 13 weeks to different levels of PCBTF. Additional animals were included for evaluation after a 13 weeks-recovery, neuropathology and toxicokinetic analyses. Hematological and clinical chemistry parameters were assessed and mortality, body weight change, organ weight were observed, as well as effects on the nervous system. Macro- and microscopic examinations were performed. A NOAEL was determined.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-α,α,α-trifluorotoluene

EC Number:

202-681-1

EC Name:

4-chloro-α,α,α-trifluorotoluene

Cas Number:

98-56-6

Molecular formula:

C7H4ClF3

IUPAC Name:

1-chloro-4-(trifluoromethyl)benzene

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 hours/day, 5 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

10 mg/m³ air (nominal)

Doses / concentrations 2

Dose / conc.:

51 mg/m³ air (nominal)

Doses / concentrations 3

Dose / conc.:

252 mg/m³ air (nominal)

No. of animals per sex per dose:

10 males and 10 females
additionally, 5/sex/group for recovery evaluation, 5/sex/group/interval for neuropathology

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: weekly
- Dose groups that were examined: all

HAEMATOLOGY: Yes
- Time schedule for collection of blood: weekly
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: no data
- Parameters checked in table [No.?] were examined. no data

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: weekly
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: no data
- Dose groups that were examined: all
- Battery of functions tested: motor activity

OTHER: organ weight, microscopic examination of liver

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

FOOD CONSUMPTION: possible but minimal and reversible decrease in food consumption (6%) at the highest test dose
ORGAN WEIGHTS: in the 252 ppm group, an 11% increase in relative liver weights was observed in both males and females.
HISTOPATHOLOGY: NON-NEOPLASTIC: centrilobular hypertrophy in 3 males and 3 females at 252 ppm

Effect levels

1

Dose descriptor:

NOEL

Effect level:

51 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: organ weights; histopathology (hepatocyte hypertrophy)

2

Dose descriptor:

LOAEC

Effect level:

252 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: organ weights; histopathology (hepatocyte hypertrophy)

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The NOEL for repeated inhalatory exposure in a 90-days study was found to be 51 ppm based on increase in relative liver weights in both sexes at highest dose tested (252 ppm) correlated with centrilobular hypertrophy.

Executive summary:

In a literature study the effects of repeated exposure of rats to PCBTF via inhalation for 13 weeks were assessed. 10 Sprague Dawley rats/sex/dose were exposed to 10, 51, or 252 ppm of the test item for 6 hours/day, 5 days/week for 13 weeks. No PCTB-related effects were observed either during exposures or weekly clinical evaluations; no changes observed in body weight gain or measured hematological and clinical chemistry parameters; increase (11%) in relative liver weights in both sexes at highest dose tested correlated with centrilobular hypertrophy. NOEL (hepatocyte hypertrophy) = 51 ppm