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Administrative data

Description of key information

Two oral acute toxicity studies are available showing LD50 > 2000 mg/kg bw.
One dermal acute toxicity study is available showing LD50 > 4600 mg/kg bw.

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
Study period:
1998-05-26 to 1998-06-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study following OECD guideline 401 but there was no certificate of analysis, no details about test substance and environmental conditions for animals
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
no certificate of analysis, no details about test substance and environmental conditions
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA-CREDO, L'Arbresle, France
- Age at study initiation: about 6 weeks old
- Weight at study initiation: 188 - 210 g for males, 173 - 181 g for females
- Fasting period before study: overnight
- Housing: 5/sex in polypropylene cages
- Diet (e.g. ad libitum): pelleted diet (UAR A04-10, Epinay sur Orge, France ), ad libitum
- Acclimation period: at least 5 days

IN-LIFE DATES: From: 1998-05-26 To: 1998-06-09
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data



Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: observed daily for clinical signs; bodyweights recorded prior to the test material administration (D1), D4, D8 and D15
- Necropsy of survivors performed: yes
Statistics:
No data
Preliminary study:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality
Clinical signs:
Six hours following administration of the test substance, a slight piloerection was observed in all animals. 1 hour after administration, a decrease in motor activity and muscle tone was noticed in one male and one female.
Body weight:
The individual growth weight of both males and females were normal. The mean weight gain in 14 days of treatment period was satisfactory (Table 1).
Gross pathology:
There were no visible organic or tissular lesions 14 days after treatment.
Other findings:
No data

Table 1: BODY WEIGHT - Individual values (g)

Animal 

D1

D4

D8

D15

D15 – D1

Sex : Male

9315

192.6

215.4

276.0

338.2

145.6

9316

192.8

207.3

263.7

323.0

130.2

9317

209.3

255.5

300.4

357.5

148.2

9318

188.9

224.1

268.6

329.7

140.8

9319

201.2

238.5

276.7

333.2

132.0

Mean

197.0

228.2

277.1

336.3

139.4

SD

8.2

19.2

14.1

13.1

8.0

Sex : Female

9320

178.1

206.6

226.0

247.7

69.6

9321

180.5

211.4

227.2

245.5

65.0

9322

176.0

195.3

214.3

234.0

58.0

9323

173.2

198.9

220.7

237.1

63.9

9324

178.9

199.8

220.9

247.9

69.0

Mean

177.3

202.4

221.8

242.4

65.1

SD

2.8

6.5

5.1

6.5

4.7

MACROSCOPIC EXAMINATION

Sex : Male

Animal 

MORTALITY

OBSERVATIONS

Day

Cause

9315

D15

Sacrifice

Normal

9316

D15

Sacrifice

Normal

9317

D15

Sacrifice

Normal

9318

D15

Sacrifice

Normal

9319

D15

Sacrifice

Normal

Sex : Female

Animal N°

MORTALITY

OBSERVATIONS

Day

Cause

9320

D15

Sacrifice

Normal

9321

D15

Sacrifice

Normal

9322

D15

Sacrifice

Normal

9323

D15

Sacrifice

Normal

9324

D15

Sacrifice

Normal

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 of the test substance is higher than 2000 mg/kg bw.
The substance is not classified according to directive 67/548/EEC and CLP regulation (EC) n° 1272/2008.
Executive summary:

An acute oral toxicity study (limit test) with the test item was conducted in 10 albino Sprague Dawley rats (5/sex/dose) under GLP conditions following OECD guideline 401. The test substance was administered through oral gavage at the single dose of 2000 mg/kg bw. Animals were observed daily for clinical signs and mortality for 14 days. Body weights were taken prior to the administration of the test material, D4, D8 and D15. Six hours following administration of the test substance, a slight piloerection was observed in all animals. 1 hour after administration, a decrease in motor activity and muscle tone was noticed in one male and one female. There was no mortality. All animals were subjected to necropsy at the end of the observation period. No gross lesions were found.

Therefore, oral LD50 of the test substance is higher than 2000 mg/kg bw. According to directive 67/548/EEC and CLP regulation (EC) n° 1272/2008, the test substance should not be classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
GLP studies following OECD guideline 401 with minor deviations, considered as appropriate and reliable to complete this endpoint.

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
Study period:
From December 9 to 24, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study conducted similarly to OECD Guideline 402 with minor deviations: no data about purity and no certificate of analysis of the test substance; no data on humidity and temperature, female animals bodyweight < 200 g at study initiation
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no data about purity and no certificate of analysis of the test substance; no data on humidity and temperature; female animals bodyweight at study initiation < 200 g
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tac:N(SD)fBR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Inc., Germantown, USA
- Age at study initiation: 6 weeks
- Weight at study initiation: Males: 249-291 g; females: 167-191 g
- Housing: Individually housed in stainless steel cages with wire mesh floors and automatic watering devices
- Diet (e.g. ad libitum): Purina Lab Chow, ad libitum
- Water (e.g. ad libitum): Filtered tap water, ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Air changes: 14/hour
- Photoperiod: 12 hours dark / 12 hours light
Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Intrascapular region
- % coverage: 30% of the body surface
- Type of wrap if used: Test sites were not wrapped; appropriate test substance was applied by syringe and gentle inunction to the clipped area and allowed to remain in contact with the skin and open air

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were not wiped after 24 hours because no excess test article was present.
Duration of exposure:
24 hours
Doses:
5 mL/kg bw
No. of animals per sex per dose:
Five
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed frequently for mortality, morbidity and overt toxic signs for the first 5 hours after dosing and twice daily thereafter for 14 days. Body weights were obtained on Days 0 and 14.
- Necropsy of survivors performed: Yes; surviving animals were sacrificed and examined grossly
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
- Clinical signs included lacrimation, diarrhea, crusty material on eyes and nose, desquamation, urine soaked fur, aggressiveness, vocalisation when touched, sore on back, and red appearance of the skin.
- No important differences in the incidence and/or nature of clinical signs between sexes were found.
Body weight:
All animals showed expected gain in bodyweight.
Gross pathology:
Findings at gross necropsy were few (yellow rectangular firm area (lobes adhered) on liver of one male) and did not reveal any test material-related trends.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the acute dermal LD50 of the test item was higher than 5 mL/kg bw therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.
Executive summary:
In an acute dermal toxicity study performed similarly to OECD guideline 402 in compliance with GLP, a group of Tac:N(SD)fBR rats (5/sex) received a single dermal dose of the test item at 5 mL/kg on clipped area of intrascapular region representing 30% of the total body surface area. The application was allowed to remain in contact with the skin and open air for 24 hours. Parameters evaluated included survival, clinical observations, bodyweight gain and necropsy findings in all animals after a 14 days observation period. No mortality was observed. All animals showed expected gain in bodyweight. Clinical signs included lacrimation, diarrhea, crusty material on eyes and nose, desquamation, urine soaked fur, aggressiveness, vocalisation when touched, sore on back, and red appearance of the skin. No important differences in the incidence and/or nature of clinical signs between sexes were found. Findings at gross necropsy were few (yellow rectangular firm area (lobes adhered) on liver of one male) and did not reveal any test material-related trends. The acute dermal LD50 was higher than 5 mL/kg bw therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 600 mg/kg bw
Quality of whole database:
LP study conducted similarly to OECD Guideline 402 with minor deviations, considered as appropriate and reliable to complete this endpoint.

Additional information

In a GLP acute oral toxicity study (limit test) performed according to OECD guideline 401, no mortality and no clinical signs related to treatment were observed, therefore LD50 was higher than 2000 mg/kg bw.

In an older study, also performed according to OECD guideline 401, the test item tested at 5000 mg/kg bw led to the following clinical signs without death: pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), diarrhea and increased salivation. LD50 was higher than 5000 mg/kg bw.

In an acute dermal toxicity study (limit test), no mortality was observed in rats exposed to 5 mL/kg bw (corresponding to 4.6 g/kg bw).


Justification for selection of acute toxicity – oral endpoint
GLP study following OECD guideline 401.

Justification for selection of acute toxicity – dermal endpoint
Only one study available for this endpoint.

Justification for classification or non-classification

As LD50 for oral and dermal acute toxicity are higher than 2000 mg/kg bw, the test item is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.