Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
April 16 to May 18, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
This IUCLID for dimethyl adipate is compiled using data from the substance itself, a structurally related compound (dimethyl glutarate) and a mixture of dibasic esters (dimethyl adipate, succinate and glutarate). The toxicity of each of these substances is similar and the document attached justifies why data on the category members can be used to support the data gaps for dimethyl adipate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
but with quality assurance documentation
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
See information in the field "Confidential details on test material"

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
Young adult male and female Crl:CD BR rats were received from Charles River Breeding Laboratories. Rats were quarantined for approximately 1 week prior to testing and were weighed and observed 3 times during the quarantine period. During the quarantine period rats were housed singly in 5” x 11" x 7" suspended, stainless steel, wire mesh cages. After exposure, rats were housed (sexes separate) either 1 or 2 per cage in 8” x 14" x 8”cages. Prior to exposure, rats’ tails and cage cards were color-coded so that individual rats could be identified after exposure. For rats housed in pairs, the rat with the lower number was identified by a slash in the right ear.

On the day of exposure, rats were approximately 7-8 weeks old; male rats weighed 238-281 g and female rats weighed 174-222 g. Except during exposure, Purina Certified Rodent Chow and water were available ad libidum. Animal rooms were maintained on a timer-controlled, 12 hour/12 hour light/dark cycle.

Environmental conditions of the animal rooms were targeted for a temperature of 23°+ 2°C and relative humidity of 50 % + 10 %. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
For the LC50 determination, groups of 5 male and 5 female rats were individually restrained in stainless steel restrainers with conical nose pieces and exposed nose-only to DBE. Each restrainer was inserted into a 38-L cylindrical exposure chamber such that only the nose of each protruded into the chamber. To determine whether the ocular response was diminished by nose-only exposure, an additional group of 4 male rats was placed in a stainless steel and aluminum wire mesh cage within the exposure chamber and exposed whole-body.

Each group of rats was exposed for a single. 4-hour period to an aerosol / vapor mixture of DBE in air. Rats were observed for clinical signs of toxicity (e.g., general physical and clinical disposition. including unusual movements, respiration. etc.) before and during exposure. upon removal from the animal restrainers approximately 30 minutes after the cessation of exposure, and daily thereafter (weekends and holidays excluded unless warranted by the rats' condition). During the exposure. the use of restrainers limited the observations mainly to the presence of nasal or oral discharges. In addition. a sharp rap was periodically delivered to the exposure chamber and rats were observed for a general startle response (rapid movement) during the exposure. This procedure was used primarily as a gross indicator of unconsciousness or death. Rats were weighed prior to exposure, and were weighed daily. weekends and holidays excluded except when warranted by the rats' condition, during the 14-day recovery period.

Atmosphere Generation

DBE was generated by atomization. Test atmospheres of DBE were generated by atomizing the liquid test material using an Airlife, Solo-Sphere Nebulizer. Conditioned, filtered houseline air (approximately 8-16 L/min) was used to generate the aerosol and to carry the aerosol directly into the 38 L cylindrical, glass exposure chamber. Located immediately inside the chamber was a plastic deflection plate (approximately 12.5 cm diameter) which acted as a baffle to promote turbulent flow and facilitate uniform distribution of the aerosol within the chamber. Chamber atmospheres were exhausted through tandem, dry-ice cold traps and an MSA activated charcoal/HEPA filter cartridge prior to discharge into a fume hood
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
3.5, 5.6, 11.0 mg/L DBE;
No. of animals per sex per dose:
5 males;
5 females;
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:starting 30 min after exposure, then daily for 14 days
- Necropsy of survivors performed: no data
- Other examinations performed: opthalmology

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 11 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No rats died following exposure to DBE at atmospheric concentrations as great as 11 mg/L, the highest concentration tested.
Clinical signs:
Clinical signs of toxicity observed in some male and female rats during the recovery period included red nasal, ocular or oral discharges, wet, yellow-stained perineum, and hunched posture. All clinical signs were transient and had resolved by study day 4.
Body weight:
Rats from all exposure groups exhibited slight to severe body weight losses 1 day after exposure (group average weight losses ranged from approximately 5-11% and 2-9% of initial body weight in male and female rats, respectively). In addition, some transient, slight to moderate weight losses occurred in some male and female rats during the first or second weeks of the recovery period.
Other findings:
Prior to exposure, the eyes of rats from the 11 mg/L group were evaluated and considered ophthalmoscopically normal. After exposure, the eyes of rats from the 3.5 or 11 mg/L groups were considered to be ophthalmoscopically normal; the corneal and pupillary reflexes were normal. At 5.6 mg/L, however, bilateral mild chemosis (edema/swelling) of the bulbar conjunctivae was found in all rats. Although a subepithelial corneal opacity was also noted in 1 rat exposed to 5.6 mg/L, this finding was believed to be due to a preexisting injury and not compound-related.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this study, the 4-hour LC50 for DBE exceeds 11 mg/L, the highest concentration tested.
Executive summary:

DBE has been tested in an acute inhalation toxicity study using Crj: CD(SD) rats, according to OECD guideline n° 403 and EU guideline n° B.2 with quality assurance documentation. 5 males and 5 females per dose were exposed to 3.5, 5.6 or 11.0 mg/L DBE for 4 h via inhalation (nose only). Clinical signs, mortality and body weight gain were checked for a period of up to 14 days after the single exposure to DBE. All animals were subjected to necropsy. No rats died following exposure to DBE at atmospheric concentrations as great as 11 mg/L, the highest concentration tested. Rats from all exposure groups exhibited slight to severe body weight losses 1 day after exposure (group average weight losses ranged from approximately 5-11% and 2-9% of initial body weight in male and female rats, respectively). In addition, some transient, slight to moderate weight losses occurred in some male and female rats during the first or second weeks of the recovery period. Clinical signs of toxicity observed in some male and female rats during the recovery period included red nasal, ocular or oral discharges, wet, yellow-stained perineum, and hunched posture. All clinical signs were transient and had resolved by study day 4. Ophthalmoscopic findings in the 5.6 mg/L group were believed to be due to a preexisting injury and not compound related as no comparable findings were seen in the 3.5 or 11 mg/L groups.

As the LC 50 is higher than 11 mg/L, DBE is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).