Registration Dossier

Administrative data

Description of key information

Single oral and dermal application of the test item to male and female rats (OECD guideline 401 and 402, GLP) did not induce treatment related mortality or symptoms of toxicity. The LD50 after oral administration is therefore considered to > 5000 mg/kg bw and > 2000 mg/kg bw after dermal application.

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:
1998-02-03 - 1998-04-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted on 24th February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA (on 12/02/97 and 1/20/98)
- Age at study initiation: Animals were born the weeks of 9/30 through 12/11/97, Experimental Start Date: 02/05/98
- Weight at study initiation: 286-300 g (males), 236 - 288 g (females)
- Housing: 5 animals/sex/cage in suspended wire cage, bedding was changed three times/week
- Diet: Fresh Purina Rat Chow, ad libitum, except for 16-20 hours prior to dosing
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: temperature-controlled animal room
- Photoperiod: 12 hours dark / 12 hours light
- Animal room was kept clean and vermin free

IN-LIFE DATES: From: 1998-02-05 To: 1998-02-19
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE:
- Concentration in vehicle: see dosage preparation
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: to make dosing by gavage possible
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED:
A single dose was administered orally by syringe and dosing needle at a dose level of 5000 mg/kg bw. All animals received the same concentration of dosing solution.

DOSAGE PREPARATION:
15 g of test item was mixed with corn oil to a total volume of 30 mL
Doses:
5000 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 and weighing: 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects
- Animals were observed twice daily for mortality
- Body weights were recorded immediately pretest, on days 3 and 7, at death or at termination in the survivors
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Nine of ten animals survived the 5000 mg/kg bw oral dose.
Clinical signs:
Red staining of the nose/mouth area was noted in the animal which died on day 1. Physical signs noted in the survivors included emaciation, chromorhinorrhea, diarrhea and red staining of the nose/mouth area.
Body weight:
Body weight changes of male survivors were normal. Weight loss, associated with an obstructed water sipper, was noted in females but all returned to normal by day 14.
Gross pathology:
Necropsy results of the animal which died on day 1 revealed that the death was due to a dosing error which resulted in the test item being deposited into the lungs rather than to a toxic effect of the test item. Necropsy results of the survivors were normal.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Guideline study (OECD TG 401) performed under GLP, Klimisch 1

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:
1998-02-03 - 1998-04-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted on 24th February 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA (on 1/27/98)
- Age at study initiation: Animals were born in the weeks of 11/16 through 11/30/1997, Experimental Start Date: 02/23/98
- Weight at study initiation: 2.4 – 2.7 kg (males), 2.3 – 2.5 g (females)
- Housing: 1 animal/sex/cage in suspended wire cages, Bedding was changed three times/week
- Diet: Fresh Purina Rabbit Chow, provided daily
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hours dark / 12 hours light
- Animal room was temperature controlled, kept clean and vermin free

IN-LIFE DATES: From: 1998-02-23 To: 1998-03-09
Type of coverage:
semiocclusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- 24 h before: Dorsal area of the trunk of each animal was clipped free of hair
- Area of exposure: approximately 10% of the body surface
- Test item was applied under a 4 layered surgical gauze patch measuring 4 x 6 inches; patch and test item were moistened with saline
- Gentle pressure was applied to the gauze to aid in the distribution of the test item
- Type of wrap: Plastic which was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was gently wiped from the dose site prior to dermal observations.

TEST MATERIAL
- Amount applied: 2000 mg/kg bw, based on the dry weight
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 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
- Toxicity and pharmacological effects: 1, 2 and 4 hours postdose and once daily for 14 days
- Mortality: twice daily for 14 days
-Test sites were scored for dermal irritation at 30 to 60 minutes post patch removal and again at 24, 48 and 72 hours post patch removal using the numerical Draize scoring code. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.
- Frequency of weighing: recorded pretest and on days 3, 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.
Mortality:
All animals survived the 2000 mg/kg bw dermal application.
Clinical signs:
Dermal reactions (including irritation) were absent on days 1, 2, 3 and 4.
Instances of diarrhea, soiling of the anogenital area, few feces and wetness of the anogenital area were noted during the observation period. Five males and three females appeared normal at each observation period.
Body weight:
Body weight changes were normal in 7/10 animals. Three animals lost weight at some time during the observation period.
Gross pathology:
Necropsy results were normal in 9/10 animals. Excess fluid in the peritoneal cavity was noted in one female.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Guideline study (OECD TG 402) performed under GLP, klimisch 1

Additional information

Acute oral toxicity

Five healthy male and five healthy female Wistar albino rats were dosed orally with the test item at 5000 mg/kg of body weight (OECD guideline 401). The rats were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pretest, on days 3 and 7, at death or at termination in the survivors. All animals were examined for gross pathology. Nine of ten animals survived the 5000 mg/kg oral dose. Red staining oft he nose/mouth area was noted in the animal which died on day 1. Physical signs noted in the survivors included emaciation, chromorhinorrhea, diarrhea and red staining of the nose/mouth area. Body weight changes of male survivors were normal. Weight loss, associated with an obstructed water sipper was noted in females but all returned to normal by day 14. Necropsy results of the animal which died on day 1 revealed that the death was due to a dosing error which resulted in the test article being deposited into the lungs rather than to a toxic effect of the test article. Necropsy results of the survivors were normal. In conclusion, the LD50 after oral administration is greater than 5000 mg/kg.

Acute dermal toxicity

Five healthy male and five healthy female New Zealand White rabbits were dosed dermally with the test item at 2000 mg/kg of body weight for 24h under occlusive conditions (OECD guideline 402). Dermal responses were recorded at 30 - 60 minutes and at 24, 48 and 72 hours post patch removal and again on days 4, 7,10 and 14. All animals were examined for gross pathology. All animals survived the 2000 mg/kg dermal application. Instances of diarrhea, soiling of the anogenital area, few feces and wetness of the anogenital area were noted during the observation period. Five males and three females appeared normal at each observation period. Dermal reactions (irritation) were absent on days 1, 2, 3 and 4. Body weight changes were normal in 7/10 animals. Three animals lost weight at some time during the observation period. Necropsy results were normal in 9/10 animals. Excess fluid in the peritoneal cavity was noted in one female. In conclusion, the LD50 after dermal application is greater than 2000 mg/kg of body weight.

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 classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008.