Diisobutyl hexahydrophthalate

Endpoint summary

Description of key information

- Acute toxicity:
Oral: LD50: >2000 mg/kg in the rat
Dermal: LD50: > 2000 mg/kg in the rat

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:

June 7-29, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted to recognised international test guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River Italia S.p.A.
- Age at study initiation:7 - 8 weeks old
- Weight at study initiation:180- 231 g
- Housing: Group hosed in polysulphone solid bottom cages
- N° of animal/cage: Up to 5/cage during acclimatisation; 3/cage during study period
- Diet: 4 RF 18 (Mucedola S.r,l)
- Diet supply: ad libitum except for an overnight fast prior to dosing and 4 hours following dosing.
- Water :ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°c +/- 2°c
- Humidity (%):55% +/- 15%
- Air changes: 15 to 25 air changes per hour
- Photoperiod: Artificial (fluorescent tubes) , daily light/dark cycle of 12/12 hours


IN-LIFE DATES: From: 2012-06-07 To: 2012-06-29

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bodyweight
- Justification for choice of vehicle: Substance non-soluble/miscible in aqueous vehicles

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION (if unusual): Admixture w/v

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Expected lack of toxcity sed on information from structurally analogous substances

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Examination of clinical signs 0.5, 2 and 4 hours after treatment and daily observations thereafter; bodyweights were determined before treatment and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

no statistics performed

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

0/6 animals

Clinical signs:

other: Salivation in 1 animal following dosing, recoveryt within 4 hours of dosing.

Gross pathology:

No abnormal findings

Other findings:

none

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acute oral toxicity of the substance has been investigated according to OECD/EU test guidelines. The LD50 was determined to be in excess of 2000 mg/kg body weight.

Executive summary:

Acute oral toxicity of the substance has been investigated according to OECD/EU test guidelines. The LD50 was determined to be in excess of 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 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

Study period:

June 12-27, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted to recognised international test guidelines

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source Charles River Italia S.p.A.
- Age at study initiation:7 - 9 weeks old
- Weight at study initiation:224 - 299 g
- Housing: policarbonatecages measuring 42 .5 x 26.6 x 18 cm with stainless stell mesh lid and floor
- N° of animal/cage: Individually caged (both during acclimatisation and study)
- cage try control: Daily inspected and changed as necessary (at least 3 times/week)
- Diet: 4 RF 18 (Mucedola S.r,l)
- Diet supply: ad libitum
- Water :ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°c +/- 2°c
- Humidity (%):55% +/- 15%
- Air changes: 15 to 25 air changes per hour
- Photoperiod: Artificial (fluorescent tubes) , daily light/dark cycle of 12/12 hours

IN-LIFE DATES: From: 2012-06-12 To: 2012-06-27

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure:approximately 10% of body surface
- Type of wrap if used:synthetic film

REMOVAL OF TEST SUBSTANCE
- Washing : After exposure , the adhesive bandage and gouze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.
- Time after start of exposure:24 hours

TEST MATERIAL
- Amount(s) applied : Aliquots were weighed accordingly to the body weight of each animal measured prior dosing
- Constant volume or concentration used: yes
- Frequency of treatment: once only , on the day of dosing
- Treatment area preparation: on the day before dosing

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days , termination on day 15.
- Frequency of observations and weighing:Observations - 1,2 and 4 hours after first dosing and daily thereafter for 14 days. Weighing - Days -1, 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: necropsy was carried out on all animals (gross necropsy examination for both internal and external abnormalities, with particular attention to the treatment site. All abnormalities were recorded.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None during 14 day post-exposure observation period

Clinical signs:

other: No signs observed considered to be of significance

Gross pathology:

No abnormal changes considered to be of significance

Other findings:

None

 

 

 

 

 

 

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute toxicity of the substance was investigated following dermal administration of a single dose to the rat at 2000 mg/kg. No mortality occurred following dosing and no signs of toxicity were observed. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

Executive summary:

The acute toxicity of the substance has been investigated following dermal administration of a single dose to the rat at 2000 mg/kg. utilising OECD/EU test methods. No mortality occurred following dosing and no signs of toxicity were observed. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

 

         

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Data are available from studies investigating effects following exposure via the oral and dermal routes of administration. No significant toxicities were apparent at limit doses of 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
Single study available for evaluation

Justification for selection of acute toxicity – dermal endpoint
Single study available for evaluation

Justification for classification or non-classification

Classification with regard to acute oral and dermal toxicity is not justified based on the observed lack of mortality at a dose level of 2000 mg/kg.