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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 453 (Combined Chronic Toxicity/Carcinogenicity Studies)
Principles of method if other than guideline:
Reproductive organs were examined in a 2-year chronic and carcinogenicity study in rats.
GLP compliance:
yes
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity > 99.9 %

Test animals

Species:
rat
Strain:
other: Crl:CD®Br
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 54 days
- Weight at study initiation: Mean male body weight week 0 was 217.6-245.6 g; mean female body weight week 0 was 159.3-166.2 g
- Fasting period before study: No
- Housing: Males and females of each concentration group were housed together and each of the four groups was housed in a separate animal room
- Diet (e.g. ad libitum): ad libitum, except during exposures
- Water (e.g. ad libitum): ad libitum, except during exposures
- Acclimation period: Approximately 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±3°C
- Humidity (%): 50±10%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
other: air
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Four 4.6 m3 stainless steel and glass chambers, quadrangular in shape with pyramidal tops and bottoms
- Method of holding animals in test chamber: Not reported
- Source and rate of air: Not reported
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: The chambers were operated in a one-pass, flow-through mode. Atmospheres were generated by metering the test substance vapours from cylinders of liquid test substance, maintained at room temperature, through rotometers into the chamber air flow. The control chamber received dilution air only.
- Temperature, humidity, pressure in air chamber: 24±5°C, 50±10%, pressure not reported
- Air flow rate: approximately 1200 L/min.
- Air change rate: Not reported
- Treatment of exhaust air: Not reported

TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatograph equipped with a programmable recording terminal. Atmospheres were measured at approximately 30-minute intervals during each 6-hour exposure with daily average concentrations for each chamber calculated from these data.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Over the 106-week exposure period, the overall means of the weekly averages for the low, intermediate, and high concentrations were all 100% of design. While 93.4, 96.3, and 100% of the individual weekly average concentrations for the low, intermediate, and high exposures, respectively, were within 10% of design, all of the weekly averages for each exposure were within 15% of design. The overall means and standard deviations of the weekly average exposure concentrations were 0.2±0.001, 1.0±0.05, and 2.5±0.06%.
Duration of treatment / exposure:
Approximately 104 weeks
Frequency of treatment:
6 hours/day, 5 days/week, excluding holidays
Duration of test:
Approximately 104 weeks
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.2, 1.0, 2.5% (v/v)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0.2±0.001%; 1.0±0.05%; 2.5±0.06%
Basis:
no data
mean and standard deviation of the weekly average exposure concentration
No. of animals per sex per dose:
30 per sex per concentration
Control animals:
yes, concurrent vehicle
Statistics:
Organ weight and final body weight data were subjected to one-way analysis of variance and Dunnett’s test. The least significant differences from control values were calculated whenever the ratio of variances (F-ratio) indicated that differences existed among the study groups. The results of histopathologic examination were analyzed by the Fisher’s Exact test for differences between control and exposed groups and by the Mantel-Haenszel test for a dose-related trend.

Results and discussion

Effect levels

Dose descriptor:
other: NOEC for reproductive organ effects
Effect level:
2.5 other: % (v/v)
Sex:
male/female
Basis for effect level:
other: No histopathological or weight effects on reproductive organs

Observed effects

No histopathological or weight effects on reproductive organs of either male or female rats were observed in a 2-year chronic and carcinogenicity inhalation study.

Applicant's summary and conclusion

Conclusions:
The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability). No histopathological or weight effects on reproductive organs of either male or female rats were observed in a 2 -year chronic and carcinogenicity inhalation study.
Executive summary:

Male and female rats were exposed, whole body, via inhalation for 6 hours a day, 5 days a week to 0, 0.2, 1.0, or 2.5% (v/v) of the test substance for 2 years. Ten rats per sex per concentration were subjected to clinical pathological evaluation after 1, 3, 6, 12, 18, and 24 months on test. An additional 10 rats per sex per concentration at 3 and 12 months on study and all surviving rats at 24 months on study were sacrificed and, together with animals found dead or sacrificed in extremis, were subjected to gross pathological examination.  All high-concentration and control animals plus all animals found dead or sacrificed in extremis were subjected to complete histopathological evaluation while only the kidneys and nasal tissues at the 3-month interim and 24-month final sacrifices, respectively, from the low- and intermediate-concentration animals were examined histopathologically. 

 

The overall means and standard deviations of the weekly average exposure concentrations were 0.2±0.001, 1.0±0.05, and 2.5±0.06%.  No histopathological or weight effects on reproductive organs of either male or female rats were observed in a 2 -year chronic and carcinogenicity inhalation study.