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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-05-10 to 1988-06-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
cited as 84/449 EWG
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): o-Chloranilin
- Physical state: yellow-orange, clear liquid
- Analytical purity: 99.6 % (IR spectroscopy)
- Impurities (identity and concentrations):
<0.01 % cyclohexylamine
<0.01 % N-isopropylaniline
<0.01 % 2-chloro-N-Isopropylanilin
0.08% aniline
<0.01% 2-Isopropylaniline
<0.01% o-nitrochlorobenzene
0.24% p-chloroaniline
<0.01% m-chloroaniline
<0.01% 2,4-dichloroaniline
<0.01% 2,5-dichloroaniline
<0.01% 2,3-dichloroaniline
<0.01% 2,3-dichloroaniline
<0.01% o-phenylendiamine
0.03 % unknown impurities
- Purity test date: 1 Feb 1988
- Lot/batch No.: Lagerkessel 15/ 594 488
- Stability under test conditions: stable throughout the test period
- Storage condition of test material: room temperature, dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: males about 10 weeks; females: 14 weeks
- Weight at study initiation: males: about 251 g; females: about 198 g
- Fasting period before study:
- Housing: macrolon cages typ II wood chips (ssniff)
- Diet: ad libitum, Altromin 1324
- Water: ad libitum, tap water
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +7- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lateral
- % coverage: 10, shaved 24 h prior to application
- Type of wrap if used: gauze, tin foil and non-irritant tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): withhand warm water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100, 500 or 2000 mg/kg body weight
- Constant volume or concentration used: no

Duration of exposure:
24 h
Doses:
100, 500 or 2000 mg/kg bodyweight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: repeated obeservation on day of application, and twice a day thereafter (once a day on week ends and holi days), weighing was done right before and 7 and 14 days after application
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, blood parameters (methemoglobin formation) in 100 mg/kg dose group

Results and discussion

Preliminary study:
no
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Mortality:
2000 mg/kg body weight: all males and four females were euthanized 6 h post-application due to moribund condition
Clinical signs:
2000 mg/kg body weight: 30 min post-application: tremor, severe cyanosis, labored breathing, poor condition, face down position, no motor
activity, 5 males and 4 females were euthanized due to animal welfare reasons, 1 female showed weaker signs of toxicity
and recovered after 2 days
500 mg/kg body weight: 1h min post-application: tremor, severe cyanosis, labored breathing, poor condition, face down position, no motor
activity but weaker than in highest dose group, recovery of all animals after 8 h
100 mg/kg body weight: no symptoms
Body weight:
2000 mg/kg body weight: reduced weight gain of the surviving female
500 mg/kg body weight: reduced weight gain of all treated animals
100 mg/kg body weight: only weak reduction in weight gain was observed in females but not males 1 week post-application
Gross pathology:
chromodakryorrhoe, severe cyanosis and dark liquid in the thoracal cavity were observed in moribund euthanized animals, bodies had the typical smell of chlorine, no pathophysiological findings were observed in the animals euthanized after the observation period of 14 d.

Any other information on results incl. tables

no further data

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information: T, R24
Conclusions:
Like other chloroanilines, the primary toxic effect of 2-chloroaniline is methaemoglobin
formation. Taking into account that humans are much more sensitive to methaemoglobin
producing substances than rats 2-chloroaniline is classified in Toxicity Category III.
Executive summary:

Bomhard, E (1988)

2-chloroaniline was tested for acute dermal toxicity equivalent to EU B.3 on 5 male and 5 female young adult wistar rats per dose level (100, 500 or 2000 mg/kg body weight) .Mortality was only observed in the highest dose level tested. There 9 of 10 animals were euthanized 6 h post-application due to their moribund condition. Following signs of toxicity were observed to decreasing extend in the 2000 and 500 mg/kg body weight dose group: tremor, labored breathing, cyanosis, face down position, poor condition and almost no motor activity. Pathophysiological changes were only evident at the highest dose level and included severe cyanosis and darl liquid in the thoracal cavity. Only the males of the 100 mg/ kg body weight dose group displayed a normal weight gain over time all over surviving test animals showed reduced weight gain one week post-application. Therefore the LD50 was calculated to be 1000 mg/kg body weight. Due to the very severe signs of toxicity the testing laboratory set the testing of additional groups aside. Based on this study 2-chloraniline should be classified as harmful in contact with skin.