Bis(2-(2-butoxyethoxy)ethyl) adipate

Endpoint summary

Description of key information

Oral (similar to OECD 401), rat: LD50 > 5000 mg/kg bw (limit test)
Dermal (OECD 402), rabbit: LD50 > 5000 mg/kg bw (limit test)

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:

21 Oct 1996 - 4 Nov 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted generally according to an accepted and published method. Experimental documentation was limited but adequate for the purposes of this summary.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

lack of details on test substance

GLP compliance:

yes

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- Source: Ace Animals, Inc., Boyertown, PA, USA- Age at study initiation: approximately 6 - 9 weeks- Weight at study initiation: 222 - 254 g- Fasting period before study: 18 hours- Housing: stainless steel, indirect bedding- Diet: Lab Diet Certified Rodent Diet #5002, ad libitum- Water: ad libitum- Acclimation period: 14 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 19 - 24 (65 - 75 °F)- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: To: 21 Oct 1996 - 4 Nov 1996

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

After 18 hours of fasting and prior to dosing, all rats (5 male: 5 female) were weighed and marked with ear clips. The weight variations of animals did not exceed ±20%. Individual doses were administered on the basis of body weight using a stainless steel intragastric feeding needle. Volumes of dose were 1.1 to 1.2 mL in all cases.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: animals were observed at 1, 3, 6 and 24 hours and daily thereafter for a total of 14 days.- Frequency of observations and weighing: at least once daily- Necropsy of survivors performed: complete gross necropsy performed on animals sacrificed at the end of the 14-day observation period. Sacrifice was accomplished via carbon dioxide asphyxiation.- Other examinations performed: animals were observed for signs of pharmacological activity and drug toxicity

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

A single male rat died by the 24 hour observation period.

Clinical signs:

other: Depression was noted in the single male animal that died. Slight depression was recorded in a single other male rat but this resolved by the 24 hour observation period. All other male rats appeared normal.Slight depression was noted in 3/5 female rats but

Gross pathology:

In 3 female rats, a red discharge was noted around the nose. The small intestines appeared moderately reddened. The stomachs appeared ulcerated.

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

CLP: not classifiedDSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study was conducted generally according to an accepted and published method. Experimental documentation was limited but adequate for the purposes of this summary.

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:

25 Oct 2012 - 19 Dec 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study. No signature.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

(1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

xxx_DRAFT REPORT_XXX

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
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: males: 8 - 9 weeks; females: 12 - 14 weeks
- Weight at study initiation: males: 231 - 250 g; females: 208 - 234 g
- Housing: individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 160812)
- Diet: Altromin 1324 maintenance diet for rats and mice (lot no. 1039), ad libitum
- Water: tap water, sulphur acidified to a pH value of approximately 2.8, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: not less than 10%
- Type of wrap if used: The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using aqua ad injectionem (Ampuva, lot no. 19FG30HA, expiry date: 06/2015)
- Time after start of exposure: 24 h

TEST MATERIAL
The test item was used as delivered by the sponsor.

Duration of exposure:

24 h

Doses:

5000 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
- Frequency of observations: several times on the day of dosing (once during the first 30 minutes and with special attention given during the first 4 hours post-dose) and once daily until the end of the observation period thereafter
- Frequency of weighing: on day 1 (prior to the application) and on days 8 and 15
- Necropsy of survivors performed: yes (in case of findings during gross pathological examination, the tissues were preserved for a possible histopathological evaluation)
- Other examinations performed: Primary Skin Irritation using the Draize Scoring System

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred throughout the study period.

Clinical signs:

other: No signs of systemic toxicity were observed throughout the study period. Signs of dermal irritation after a single dose application were noted in females only: scratches (2/5) on Days 7-11; desquamation (1/5) on Days 7-11; eschar (1/5) on Days 9-11. Howev

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Additional information

Acute toxicity: via oral route

The available key study (Nitka, 1997) was conducted according to the EPA OTS 798.1175 test guideline (simillar to OECD 401) and in compliance with GLP (limit test). Five Wistar rats per sex received the undiluted test item by oral gavage at the limit dose of 5000 mg/kg bw. A single male rat died during the 14-day observation period and showed depression before death. Slight depression was recorded in a single other male rat, but this resolved by the 24 hour observation period. All other male rats appeared normal. Slight depression was noted in 3/5 females, which resolved within 24 h post dosing. Red anal and urethral discharges were noted, with peri-anal hair loss, which was resolved in all animals by observation day 13. Body weight gain was as expected in all animals. Based on these results, the oral LD50 was determined to be >5000 mg/kg bw for both male and female rats.

Acute toxicity: via inhalation route

No data available (exposure based waiving).

Acute toxicity: via dermal route

The available key study (Schmid, 2013) was conducted according to the OECD 402 and in compliance with GLP (limit test). The shaved dorsal skin of 5 Wistar rats per sex was exposed to the undiluted test substance at a limit dose of 5000 mg/kg bw for 24 h under semiocclusive conditions. After removal of the test substance, animals were observed for a period of 14 days. No mortality and no clinical signs of toxicity were observed up to the end of the observation period. Signs of slight dermal irritation were noted in females only, including scratches (2/5), desquamation (1/5) and eschar (1/5). The body weight development of all male and female animals was within the expected range. Necropsy revealed no substance-related findings. Based on these results, the dermal LD50 was determined to be >5000 mg/kg bw for both male and female rats.

Justification for selection of acute toxicity – oral endpoint
The key study was selected for assessment.

Justification for selection of acute toxicity – dermal endpoint
The key study was selected for assessment.

Justification for classification or non-classification

The available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.