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Administrative data

Description of key information

The acute oral LD50 value for read-across substance, bis(2-ethylhexyl) adipate, was determined to be ca. 19100 mg/kg bw.

The acute oral LD50 value for read-across substance, diisononyl adipate, was determined to be > 5000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
Please see Section 13 below.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
Please see Section 13 below.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 19 100 mg/kg bw
Remarks on result:
other: converted from 20.7 cm3/kg
Interpretation of results:
GHS criteria not met
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: Non-GLP, near guideline study, adequate for assessment.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: white rat
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Doses:
Doses oral toxicity: 40, 32, 25, 20, 16, 13, 10, 8, 4, 2, 1 and 0.5 cm3/kg
No. of animals per sex per dose:
No. of animals per sex per dose (M=Male; F=Female):
Dose 40: (5F), 32: (1M/4F), 25 (5F) , 20: (5F), 16: (1M, 4F), 13: (5F), 10: (5M), 8: (5M), 4: (1M), 2: (1M), 1: (1M) and 0.5: (1M).
Control animals:
no
Details on study design:
Examinations performed: lethality, LD50, clinical signs and findings, body weight, pathology.
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 19 100 mg/kg bw
Remarks on result:
other: converted from 20.7 cm3 /kg
Mortality:
Dead rats/total rats per doses oral toxicity (cm3/kg):
Dose 40: 5/5
Dose 32: 3/5
Dose 25: 4/5
Dose 20: 4/5
Dose 16: 1/5
Dose 13: 2/5
Dose 10: 1/5
Dose 8: 0/5
Dose 4: 0/1
Dose 2: 0/1
Dose 1: 0/1
Dose 0.5: 0/1
(Animals were observed for 14 days in total)
Clinical signs:
other: High dose: (amongst others:) Apathy, Diarrhea, loss of apetite, followed by lethality. Mid dose: (amongst others:) loss of weight, Diarrhea, loss of apetite. Low dose: (amongst others:) Apathy, loss of apetite.
Gross pathology:
Not given
Interpretation of results:
GHS criteria not met
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: Near-guideline study, acceptable for assessment.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 218 g; female 188 g
- Fasting period before study: 16 hours
- Diet: ad libitum
- Water : ad libitum
- Acclimation period: at least one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:
Doses:
single dose of 5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days
Statistics:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No mortality occured.
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:
Klimisch 2

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
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
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:
01-jul-2010 to 15-jul-2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx.11 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.

Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 – 21.6ºC
- Humidity (%): 42 - 79%
Temporary deviations from the maximum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 01-jul-2010 to 15-jul-2010
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.



Duration of exposure:
24 hours.
Doses:
2000 mg/kg (2.17 mL/kg) body weight.

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Dose level (volume): 2000 mg/kg (2.17 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity.

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: none.
Statistics:
None.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 exceeds 2000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
other: Chromodacryorrhoea (snout) was noted for all males and two females on Day 1 and/or 2. Flat posture was observed for two males on Day 1. No clinical signs were noted for three females. Scales were seen in the treated skin-area of one male on Day 5.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of Diisodecyl adipate in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Diisodecyl adipate does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch 1 study

Additional information

Justification for classification or non-classification

Based on the results for acute oral and acute dermal toxicity, Diisodecyl adipate does not have to be classified and has no obligatory labelling requirement for acute oral or acute dermal toxicity according to the CLP Regulation (EC) No 1272/2008.