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Description of key information

An acute oral toxicity study with rats was performed according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) and GLP guidelines. Three female rats were dosed with 2000 mg/kg bw of the test substance, followed by three additional female rats. No deaths occurred. No clinical signs were noted and no remarkable body weight changes occurred. Gross pathology did not reveal any abnormalities in the examined organs and tissues. Based on the results of this study, the estimated oral LD50 is greater than 2000 mg/kg.

An acute dermal toxicity test was conducted with five male and five female rats following OECD and EPA guidelines according to GLP principles. No mortality occurred and no clinical signs were noted. No unexpected changes in body weight gain were reported. Dermal findings noted during the study consisted of very slight (grade 1) to slight (grade 2) erythema and desquamation and were reverted from day 8 onwards. Based on these results, the test substance has an acute LD50 > 2000 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:
2013 March 07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD guideline and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
Identifier: EXP1200078
Appearance: Very dark brown (almost black) viscous liquid
Batch: E00275-350
Sample Expiration Date: end-2013
Purity:100%
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Laboratories, Inc., Raleigh, NC, USA.
- Age at study initiation: Young adult animals (approx. 11 weeks old).
- Weight at study initiation: Body weight values ranged from 214 g to 253 g.
- Fasting period before study: Yes, 18-20 hours prior to dosing, food was returned approximately four hours after dosing.
- Housing: Individually in clean, stainless steel, wire-mesh cages.
- Diet: Free access to pelleted rodent diet (PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002).
- Water: Free access to tap water.
- Acclimation period: At least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 - 21.6
- Humidity (%): 43.9 - 53.7
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 October 2012 to 09 November 2012
Route of administration:
oral: gavage
Vehicle:
other: mineral oil
Details on oral exposure:
GAVAGE METHOD:
- Not specified.

Frequency:
- Single dosage, on Day 1.

VEHICLE:
- Mineral oil (manufactured by Spectrum Chemical Manufacturing Corp., Gardena, CA; Lot no. 2AB0895; expiration date 16 May 2013).

MAXIMUM DOSE VOLUME APPLIED:
- 2000 mg/kg based on a dose concentration of 400 mg/mL and dose volume of 5 mL/kg.

DOSAGE PREPARATION:
- On the day of dosing, an appropriate amount of the test substance was weighed and added to a sufficient volume of mineral oil in a storage container. The test substance formulation was stirred throughout use with a magnetic stirrer.
Doses:
2000 mg/kg body weight.

No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Rats were observed at approximately 15 minutes and 1, 2 and 4 hours post-dosing on study day 0 and twice daily, once in the morning and once in the afternoon, thereafter for 14 days.
Body weights: Body weights were obtained and recorded on study days 0 (initiation), 7, and 14 (termination).
Clinical signs: Rats were observed at approximately 15 minutes and 1, 2, and 4 hours post-dosing on study day 0 and once daily thereafter for 14 days.
- Necropsy of survivors performed: On study day 14, all rats were euthanized by carbon dioxide inhalation. The major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No significant clinical signs were noted up to 14 days after dosage.
Body weight:
There were no remarkable body weight changes noted during the study.
Gross pathology:
There were no macroscopic findings at the scheduled necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD test guideline 423, for EXP1200078 an LD50 of >2000 mg/kg bw was determined.
Executive summary:

An acute oral toxicity study with rats was performed according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) and GLP guidelines. Three female rats were dosed with 2000 mg/kg bw of the test substance, followed by three additional female rats.

No deaths occurred. No clinical signs were noted and no remarkable body weight changes occurred. Gross pathology did not reveal any abnormalities in the examined organs and tissues.

Based on the results of this study, the estimated oral LD50 of EXP1200078 is greater than 2000 mg/kg. EXP1200078

is not classified for acute oral toxicity according to EC regulation No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Modern reliable study, conducted to GLP standard (Klimiisch 1)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study technically not feasible
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Executive summary:

The study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapor pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

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:
October 2012- March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and EPA guidelines according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Identifier: EXP1200078
Appearance: Very dark brown (almost black) viscous liquid
Batch: E00275-350
Sample Expiration Date: end-2013
Purity:100%
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, NC
- Age at study initiation: appr. 11 weeks
- Weight at study initiation: 318 to 428 g (males) and 221 to 263 g (females)
The males weighed more than recommended in the OECD guideline, but this deviation did not influence the study outcome.
- Fasting period before study: no
- Housing: individually in stainless steel, wire-mesh cages
- Diet: ad libitum (PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002)
- Water: ad libitum (municipal water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 to 21.6
- Humidity (%): 43.9 to 49.5
- Air changes (per hr): 10 (minimum)
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25OCT2012 To: 08NOV2012
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: appr. 10% (to unabraded skin)
The test substance was applied to the same area for each animal based on a target area established using the body weight of the first animal/sex. As a result, areas of coverage for 3 male and 4 females were calculated to be 9.7%, 9.1%, 8.9%, 9.1%, 8.9%, 9.5%,
and 9.9%, of the total body surface, respectively. This deviations did not negatively impact the quality or integrity of the data nor the outcome of the study.
- Type of wrap if used: gauze binders secured with nonirritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: exposure sites were wiped with disposable paper towels moistened with tepid tap water and 1% Ivory® soap solution
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2.1 mL/kg (2.0 g/kg)
- Constant volume or concentration used: no
Duration of exposure:
24 hours
Doses:
2000 mg/kg
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 and weighing: mortality and clinical signs were checked twice daily and 1, 2, and 4 hours post-application. Weighing was done at day 0, 7 and 14.
- Necropsy of survivors performed: yes, major organ systems of the cranial, thoracic, and abdominal cavities were examined.
- Other examinations performed: dermal observations (30-60 minutes after bandage removal and daily thereafter) according to Draize.
Statistics:
None performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical findings observed during the study.
Body weight:
4/5 females had slight body weight loss from day 0-7, gain was noted from day 7-14.
For all other animals no remarkable body weigt changes were noted.
Gross pathology:
There were no macroscopic findings noted at the scheduled necropsy.
Other findings:
One male showed slight erythema on day 7. Two females had erythema scores of 1 and/or 2 starting on day 4 and up to day 7. One female showed desquamination on days 4-7. No edema was observed. Residual test article was observed within dose sites of all animals, up to day 2-4.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal toxicity of EXP1200078 was tested according to OECD/ EPA guidelines acording to GLP principles. The LD50 was determined to be >2000 mg/kg bw.
Executive summary:

An acute dermal toxicity test was conducted with five male and five female rats following OECD and EPA guidelines according to GLP principles. EXP1200078 was applied semi-occlusively at 2000 mg/kg bw for 24 hours. No mortality occurred and no clinical signs were noted. No unexpected changes in body weight gain were reported. Dermal findings noted during the study consisted of very slight (grade 1) to slight (grade 2) erythema and desquamation and were reverted from day 8 onwards.

Based on these results, the test substance has an acute LD50 > 2000 mg/kg bw and is not classified for acute dermal toxicity according to EC regulation No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Modern reliable study, conducted to GLP standard (Klimiisch 1)

Additional information

The inhalation study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapor pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for classification or non-classification

The OECD 423 and 402 studies showed LD50 values >2000 mg/kg for the registration substance. In accordance with Regulation (EC) No. 1272/2008 the registration substance does not require hazard classification for acute toxicity.