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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11.03.1987 - 03.07.1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
α,2-dichlorotoluene
EC Number:
210-258-8
EC Name:
α,2-dichlorotoluene
Cas Number:
611-19-8
Molecular formula:
C7H6Cl2
IUPAC Name:
1-chloro-2-(chloromethyl)benzene
Details on test material:
Source: HOECHST AG- Code: GLAC 405- Purity: >99%

Test animals

Species:
rat
Strain:
other: Wistar, Hoe: WISKf(SPF71)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, SPF-breeding
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation:
males: mean 201 g (217 - 184 g), n =30
females: mean 199 g (209 - 177 g), n =30
- Fasting period before study:
- Housing: 5 rats of same sex in Makrolon cages with softwood granulate material
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not less than 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel-glass cylinder
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: zylindric cages, headnose exposition
- Source and rate of air: 800 L/h
- Method of conditioning air: substance injection into the spray valve:
Group 1: 2 mL/h
Group 2: 6 mL/h
Group 3: 12 mL/h
Group 4: 22.5 mL/h
Group 5: 60 mL/h
Group 6/7: 90 mL/h
- System of generating particulates/aerosols: Compressed air (pressure: 4 bar) passed a spray valve (800 L/h) to obtain a primary aerosol
in a 10 L four-necked round-bottomed flask. Secondary aerosol reached the inhalation chamber by a rise pipe.
Air is exhausted at the bottom of the inhalation chamber.
- Method of particle size determination: no data
- Treatment of exhaust air: different filter and washing bottles (10% NaOH, CaCl2)
- Temperature, humidity, pressure in air chamber: modest low pressure (aeration: 800 L/h; exhaust: 1100 L/h)


TEST ATMOSPHERE
- Brief description of analytical method used:
The active ingredient is absorbed in n-hexane. N-hexane is cooled by a mixture of methanol/carbondioxide.
The hexane solution is analyzed with GC-FID, using an external standardization.
- Samples taken from breathing zone: no data

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.587, 1.548, 1.648, 2.716, 5.268 or 5.723 (4.545) mg/L o-Chlorobenzylchloride
The value 4.545 mg/L was replaced by the value 5.732 mg/L, which was used for LC50 calculation.
It was obtained under identical conditions, but without animals (group 7).
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
30 male and 30 female Wistar rats were used. Rats were allocated to 1 of 6 dose groups, each of 5 males and 5 females.
The rats were observed during exposure and at least twice daily throughout the 14-day observation period.
During the observation period all rats were weighed at day 7 and 14 post treatment.
At the end of the 14-day observation period, the rats were sacrificed by an overdose of Nembutal except
those animals which showed ongoing symptoms.
Dead and sacrificed rats were subjected to a detailed macroscopic examination.
Statistics:
Probit analysis

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2.8 mg/L air
Based on:
test mat.
95% CL:
1.98 - 4.18
Exp. duration:
4 h
Mortality:
Dose 0.587 mg/L: males 0/5; females 0/5 : cumulative 0/10
Dose 1.548 mg/L: males 1/5; females 2/5 ; cumulative 3/10
Dose 1.648 mg/L: males 3/5; females 2/5 ; cumulative 5/10
Dose 2.716 mg/L: males 1/5; females 1/5 ; cumulative 2/10
Dose 5.268 mg/L: males 3/5; females 3/5 ; cumulative 6/10
Dose 5.723 mg/L: males 5/5; females 5/5 ; cumulative 10/10

Deaths occurred in between day 1 and day 44 post beginning of treatment.


Clinical signs:
other: Gasping respiration, respiratory sounds, uncoordinated, ataxic and stilted gait, cyanosis, stupor, squatting posture, prone position, flanks pinched in, nose and lid margin red-encrusted, corneal opacity, and narrow palpebra fissure. Except two females of
Body weight:
All surviving animals had exceeded their primary weights.
Gross pathology:
Macroscopic examination of perished rats revealed red coloured lungs. Pulmonary section resulted in discharge of a clear fluid and of foam.
Sporadically beige spots on liver and inflated small intestine were observed.
Except the two females killed at day 56 none of the rats sacrificed at the end of the observation period showed any macroscopic abnormalities.

Any other information on results incl. tables


Table 1. Mortality during observation period:
=======================================================
Dose (mg/l)      males     females     cumulative
0.587            0 / 5     0 / 5       0 / 10
1.548            1 / 5     2 / 5       3 / 10
1.648            3 / 5     2 / 5       5 / 10
2.716            1 / 5     1 / 5       2 / 10
5.268            3 / 5     3 / 5       6 / 10
5.723            5 / 5     5 / 5       10 / 10
=======================================================

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information R20: Harmful by inhalation / GHS: Cat. 4 Criteria used for interpretation of results: EU
Conclusions:
LC50 Combined = 2.80 mg o-Chlorobenzylchloride/L air
Executive summary:

A study on acute inhalation toxicity in rats was carried out under OECD GL 403 in compliance with GLP. Rats (5 animals/sex/group) were exposed (headnose) continuously for 4 hours to o-Chlorobenzylchloride aerosol at concentrations of 0.587, 1.548, 1.648, 2.716, 5.268 and 5.723 mg/L, and observed for 14 days. Death occurred at 1.548 mg/L and higher. The LC50 value was estimated to be 2.8 mg/L in both sexes. Clinical signs observed were gasping respiration, respiratory sounds, uncoordinated, ataxic and stilted gait, cyanosis, stupor, squatting posture, prone position, flanks pinched in, nose and lid margin red-encrusted, corneal opacity, and narrow palpebra fissure.

 

LC50 Males       = 2.80 mg/L (confidence level p=0.05: 1.55 – 5.48 mg o-Chlorobenzylchloride/L air)

LC50 Females   = 2.80 mg/L (confidence level p=0.05: 1.55 – 5.47 mg o-Chlorobenzylchloride/L air)

LC50 Combined = 2.80 mg/L (confidence level p=0.05: 1.98 – 4.18 mg o-Chlorobenzylchloride/L air)