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Administrative data

Description of key information

2,3-Epoxypropyl neodecanoate, oligomeric reaction products with toluene-4-sulfonic acid is of low oral and inhalation toxicity with an oral LD50 (rat) of > 10000 mg/kg bw (OECD 401, Hüls AG, 1985) and an inhalation LC50 of > 1900 mg/ m3 (OECD 403, Seibersdorf 2011)

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:
1985-11-23 to 1985-12-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Strain: Wistar (Bor: WISW (SPF TNO))
- Source: Winkelmann, Borchen (Germany)
- Weight at study initiation: females 153 g, males 206 g (mean)
- Fastening before administration: 16 hours
Environmental conditions: - Feed: R 10 complete feed for rats (Ssniff, Soest; Germany)
- Water: tap water ad libitum
- Room temperature: 20°C (+/- 1°C)
- Humidity: 60% (+/- 5%)
- Air change: 15 times per hour
- Illumination: 12 hour light/dark rhythm
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test item was administered undiluted. Rats were fasted for 16 hours and then received a single oral dose by gavage: Volume 9.488 mL/kg bw.
Doses:
- Doses: 10000 mg/kg body weight, volume: 9.488 mL/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Post dose observation period: 14 days
EXAMINATIONS:
- body weight: before and on days 1, 7, 14 after treatment
- clinical signs: up to 6 hours after treatment, then daily
- gross pathology at the end of investigation
Statistics:
not necessarry
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
After 1-2 hours some animals had ruffled fur ans one animal diuresis, after 4 hours ruffled fur was observed in 9 animals and diuresis in 10 animals, and later some of them showed staggering gait, slight ataxia and sedation, diarrhoe and a squatting position.While after 24 hours diuresis was stillobserved in 9 animals, all of them were free from the symptoms of poisoning after 48 hours.
Body weight:
Increase of body weight was unaffected by the treatment.
Gross pathology:
Dissection at the end of the experiment revealed hyperaemia of the gastric mucosa in 5 animals and additionally in one animal partial hyperaemia of the small intestinal mucosa
Other findings:
no further information

no further remarks

Conclusions:
Under the conditions of this study, the acute toxicity of the test item in male and female rats is greater than 10000 mg/kg body weight.
Executive summary:

In a determination of the acute oral toxicity in a limit test of test item 5 male and 5 female rats received a single oral dose by gavage of 10000 mg/kg body weight. After 1-2 hours some animals had ruffled fur and one animal diuresis, after 4 hours ruffled fur was observed in 9 animals and diuresis in 10 animals, and later some of them showed staggering gait, slight ataxia and sedation, diarrhoe and a squatting position.While after 24 hours diuresis was still observed in 9 animals, all of them were free from the symptoms of poisoning after 48 hours. The increase of body weight was unaffected by the treatment. Dissection at the end of the experiment revealed hyperaemia of the gastric mucosa in 5 animals and additionally in one animal partial hyperaemia of the small intestinal mucosa

Under the conditions of this study, the acute toxicity of test item in male and female rats is greater than 10000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
10 000 mg/kg bw
Quality of whole database:
The study is valid without restriction (Klimisch code 1)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-10-07 to 2011-10-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
2009
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
1998
GLP compliance:
no
Remarks:
(Lab. closed before GLP-Konformation)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS: 
- Strain: Rattus norvegicus) / CD / Crl: CD(SD)
- Source: Charles River Laboratories, 97633 Sulzfeld, Germany
- Age: 8 to 9 weeks at time of administration
- Weight at study initiation: males: 317.4 g, females: 244.9 g
- Number of animals: 5 males and 5 females
- Housing: single caging
- Diet: ad libitum, ssniff R/M-H V 1534
- Water: ad libitum, tab water
- Acclimatisation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): mean 20.8 °C
- Humidity (%): mean 41.7 %
- Photoperiod (hrs dark / hrs light): 12 hours darkness, 12 hours artifical light
- Air exchange: about 12/h
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Type of exposure: nose-only, using a Head Nose Only Exposure Unit from TSE-Systems GmbH, Bad Homburg, Germany
- Method of holding animals in test chamber (volume 24 l): In ten openings of the chamber, the inhalation tubes with the animals were situated.
- Type or preparation of particles: For aerosol generation am aerosol nozzle was used. Test substance – ethanol mixtures (1+9) were dosed with a
syringe pump and sprayed by an nozzle. The desired aerosol concentrations were obtained by controlling the feed rate of the syringe pump. The
nozzle was placed into a separator which was fixed on the upper centre of the inhalation chamber. Larger droplets sediment within the separator
and smaller ones followed the air stream to the outer chamber and reached the animals
- Method of particle size distribution: The size of the aerosol particles was analysed twice during the exposure with a cascade impactor
(Berner-Impaktor Type LPI4/0,06/2 from Hauke KG, Gmunden, Austria). It contains nine steps with cut-off- diameters from 0.06 µm to 16 µm.
The cut-off diameters were obtained from the manufacturer. 5.65 litres/minute of the test substance - air mixture were passed through the
impactor and the amount which sediment in the individual steps was determined gravimetrically. The site of collection was the same as for the
analysis.
The calculated mass median aerodynamic diameter (MMAD) of the test substance aerosol was 2.0 and 1.96 µm.
- Temperature, humidity: T: 19.3 to 19.7°C, H: 47.5 % to 47.9 %
TEST ATMOSPHERE
- Concentrations: 1.9 mg/l, the maximal obtainable aerosol concentrations were only about 1.9 mg/L and therefore below the limit concentration of 5 mg/L.
- Flow (L/min): 5.65 litres/minute of the test substance - air mixture were passed through the impactor
- Air flow: 17.2 L/min

Analytical verification of test atmosphere concentrations:
yes
Remarks:
The concentration of the aerosol was detected 7 times during the exposure period
Duration of exposure:
4 h
Remarks on duration:
4 hours
Concentrations:
The mean actual aerosol concentration was 1.9 mg/L.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
EXAMINATIONS: 
- Post dose observation period: 14 days
- body weights: before,  1, 7 and 14 days after treatment   
- behavior/clinical signs/mortality: 1, 2, 3, 4, 5, and 6 hours after start of exposure and then at least once a day for a total of 14 days 
- Necropsy: Surviving animals were killed by CO2-asphyxia (80 % CO2 and 20 % air) and subjected to a necropsy including a gross pathological
examination.
Statistics:
not necessary
Preliminary study:
Before starting the test, the following experiments were made to obtain more information about the test substance:
- It was tried to produce an aerosol with an actual concentration of about 5 mg respirable test substance per litre.
- Two animals were exposed to an aerosol of the test substance to get first information about its possible toxicity.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.9 mg/L air
Exp. duration:
4 h
Mortality:
All animals survived till the end of the study.
Clinical signs:
No abnormal observations were seen in any animal during the 14 days observation period.
Body weight:
The body weight and weight gain was inconspicuous in all animals. The body weight loss the first days after the expose which was seen in most
animals is caused by the restraining in the inhalation tube and not necessarily test substance related. No adverse effect of the test substance can
be derived from the body weight data.
Gross pathology:
Nothing abnormal was seen in any of the animals.
Other findings:
no other findings

no further remarks


Conclusions:
The LC50, per inhalation, four hours exposure, of test item for male and female rats is therefore greater than 1.9 mg/L air which is the highest technically feasible aerosol concentration.
Executive summary:

It was the aim of this study to reveal acute toxic effects of test item after a single administration per inhalation as a liquid aerosol.

Test item was administered as aerosol with a mass median aerodynamic diameter of 2.0µm per inhalation to Sprague Dawley rats. The test substance was applied for 4 hours in a nose-only inhalation device. The actual concentration of the aerosol was1.9mg per litre air which is under the limit concentration for this kind of tests. Five male and fivefemale animals were exposed. The inhalation exposure of rats to test item at the maximal technically feasible concentration of 1.9 mg/L did not produce signs of toxicity. All animals survived and no adverse effects were observed during the 14-day observation period.

The LC50, per inhalation, four hours exposure, of test item for male and female rats is therefore greater than 1.9 mg/L air which is the highest technically feasible aerosol concentration.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
1 900 mg/m³
Quality of whole database:
The study is valid without restriction (Klimisch code 1)

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

2,3-Epoxypropyl neodecanoate, oligomeric reaction products with toluene-4-sulfonic acid is of low oral and inhalation toxicity with an oral LD50 (rat) of > 10000 mg/kg bw (OECD 401, Hüls AG, 1985) and an inhalation LC50 of > 1900 mg/ m3 (OECD 403, Seibersdorf 2011).


Justification for selection of acute toxicity – dermal endpoint
According to REACH Annex VIII (Column 2 of section 8.5.3) acute dermal study not needed because inhalation is considered to be the relevant route of exposure during use.

Justification for classification or non-classification

According to the criteria of EC Directive 67/548/EEC and EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures and based on the results of the studies

2,3-Epoxypropyl neodecanoate, oligomeric reaction products with toluene-4-sulfonic acid

is not classified.