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Administrative data

Description of key information

- LD50 acute oral toxicity (male and female; rat): > 7,750 mg/kg bw (BASF, 784965, 1978; reliability score: 2)

- LD50 acute dermal toxicity (male and female; rat): > 2000 mg/kg bw (BASF, 934003, 1993; reliability score: 1 (OECD 402))

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline methods with acceptable restrictions - analytical purity of test article was not given in the report
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(dosing volume > 10 mL/kg bw, 10/14 hour light/dark cycle, acclimation period = 4 days)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name as cited in publication: 2 - [2' hydroxy - 3', 5' - bis- (alpha, aplha dimethylbenzyl) phenyl]-benzotriazole
- Batch number: A 16-234/5
- Analytical purity: no data
- Physical state: solid
Species:
rat
Strain:
other: Tif RAI f (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba Geigy Ltd.
- Age: 7 to 8 wks
- Mean weight range at study initiation: 173 - 187 g (♂) and 175 - 184 g (♀)
- Fasting period before study: overnight
- Housing: 5/cage (macrolon cages type V)
- Diet: ad libitum; NAFAG Gossau SG
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 14/10

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
(400)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10, 20, 30 %
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: Test substance is insoluble in water

MAXIMUM DOSE VOLUME APPLIED: 10 - 25.8 mL/kg bw

DOSAGE PREPARATION
A test substance suspension was prepared. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Doses:
1,000, 2,150, 4,640 and 7,750 mg/kg bw
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: Physical condition and rate of deaths were monitored throughout the whole observation period.
- Frequency of weighing: body weights were recorded immediately prior to dosing (control weights) and 7 and 14 days post treatment
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 750 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Highest dose tested. Mortality did not occur in any dose group.
Mortality:
No mortality was detected in any group
Clinical signs:
- 1,000 mg/kg bw: sedation, dyspnoea, exophthalmos, ruffled fur and curved body position (symptoms starting as early as 1 hour post dosing, fully reversible within 8 days)
- 2,150 and 4,640mg/kg bw: sedation, dyspnoea, exophthalmos, ruffled fur and curved body position (symptoms starting as early as 1 hour post dosing, fully reversible within 10 days)
- 7,750 mg/kg bw: sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea and curved body position (symptoms starting as early as 1 hour post dosing, fully reversible within 8 days)

Body weight:
see table 1
Gross pathology:
No substance related gross organ changes were seen at the necropsy of sacrificed animals

Table 1: Table of Body weights (acute oral toxicity)

 

 

Dose (mg/kg bw)

 

 

1,000

2,150

4,640

7,750

Day 1

187 ± 7.1

173 ± 2.3

175 ± 3.7

181 ± 1.6

184 ± 4.1

179 ± 1.3

175 ± 2.8

163 ± 4.5

Day 7

251 ± 9.6

233 ± 9.8

250 ± 8.3

237 ± 1.8

219 ± 6.1

216 ± 5.2

210 ± 7.5

194 ± 6.6

Day 14

289 ± 17.0

285 ± 11.6

298 ± 17.2

288 ± 8.7

248 ± 7.0

239 ± 4.0

233 ± 9.7

217 ± 7.0

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
7 750 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline (OECD 402) study, GLP study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(Feb. 1987)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba Geigy Ltd. Animal Production, 4332 Stein/ Switzerland
- Age at study initiation: young adult
- Weight at study initiation: 212 -237 g
- Housing: individually; in Macrolon type 3 cages
- Diet: Rat diet (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland); ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % (w/v) in 0.1 % (w/v) aqueous polysorbate 80
Details on dermal exposure:
TEST SITE
- Shaving: approx. 24 hours before treatment
- Area of exposure: back
- % coverage: at least 10 %
- Type of wrap if used: gauze-lined dressing was fastened around the trunk with an adhesive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: yes (water)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 4 mL/kg bw
- Concentration (if solution): no data
Duration of exposure:
24 hours
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality was monitored twice daily on week days and once on weekends. Clinical signs were monitored daily
- Frequency of weighing: immediately before application and on days 7 and 14
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Highest dose tested. No mortality occurred and the only clinical sign manifested was piloerection (fully reversible within 1 day)
Mortality:
No mortalities occurred.
Clinical signs:
- Slight piloerection was seen. This is common symptom in acute dermal tests. The animals recovered within 1 day.
Body weight:
Individual body weight, their group means and standard deviations were normal and comparable to that of rats of this strain and age (see table 1)
Gross pathology:
At necropsy, no deviations from normal morphology were found.

Table 1: Table of mean body weights (n = 5); acute dermal toxicity

 

 

Dose

 

 

2,000 (mg/kg bw)

Day 0

219 ± 6.1

223 ± 9.0

Day 7

269 ± 10.7

248 ± 14.0

Day 14

319 ± 9.3

266 ± 15.7

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Acute oral toxicity

In a standard acute oral toxicity study performed similarly to OECD TG 401, groups (5 rats/ dose/ sex) of 7 - 8 weeks old Tif Rai f (SPF) rats were administered the test substance (no data on purity) via gavage after an overnight fasting period. The test substance was administered at doses of 1,000, 2,150, 4,640 and 7,750 mg/kg bw in polyethylene glycol (400). Animals were subsequently observed for a period of 14 day in which time clinical signs of toxicity, body weights changes and cases of mortality were noted. 

Death did not occur at any dose level. Hence the LD 50 is higher than 7,750 mg/kg bw. Registered clinical signs of toxicity seen in all groups were sedation, dyspnoea, exophthalmoses, ruffled fur, curved body position and diarrhoea (seen in the highest dose only). Clinical signs were fully reversible within 10 days in all animals. Body weight development was normal and at necropsy, no deviations from normal morphology were found.

This study is suitable for assessment of acute oral toxicity as it was performed using a protocol which is similar and equivalent to the obsolete OECD 401 guideline.

Acute dermal toxicity

In an acute dermal toxicity study, groups of young adult Tif RAI f (SPF) rats, 5/ sex/ dose were dermally exposed to the test substance (> 99 % pure) in 0.5 % (w/v) carboxymethyl cellulose in 0.1 % (w/v) aqueous polysorbate 80 for 24 hours to at least 10 % of the total body surface at the limit dose of 2,000 mg/kg bw. Substance application was performed under a semi-occlusive dressing. Animals then were observed for 14 days. 

No mortalities occurred. LD 50 thus lies higher than 2,000 mg/kg bw. Treatment related clinical signs of toxicity were limited to piloerection which was fully reversible within 1 day. There were no treatment related necropsy findings or changes in body weight. 

This study is suitable for assessment of acute dermal toxicity as it was performed according to OECD 402 (1987) and GLP standards.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification. Based on the criteria laid down in Regulation (EC) No.1272/2008, as amended for the fifth time in Directive EC 944/2013, classification for acute toxicity is not warranted.