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Description of key information

GLP-studies according to OECD guidelines 401 and 402 are available for dipropylene glycol methyl ether acetate.  In addition, non-GLP studies equivalent to OECD guideline 403 are available.

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:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to GLP and meets OECD and EEC guideline requirements.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Manston Road, Margate, Kent
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 151-210 g
- Fasting period before study: 19-20 h before dosing and for 1.5-2.5 h post dosing
- Housing: The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum of 6 animals per cage for the dose ranging study and 5 animals per cage for the main study
- Diet (e.g. ad libitum): The rats were fed Expanded Rat and Mouse Maintenance Diet
- Water (e.g. ad libitum): Tap water was available ad libitum throughout the study
- Acclimation period: The rats were allowed an acclimatisation period of at least 9 days before test commencement.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean environmental maximum and minimum temperatures were 21ºC and 19 ºC
- Humidity (%): Mean relative humiodity was 40%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle (light hours 0700-1900 h)


IN-LIFE DATES: From: 15 February 1990 To: 07 March 1990
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
On the day of dosing, T-4388 was freshly prepared in corn oil. The test material was administered orally in a single dose by means of a gavage at a constant dose volume of 10 ml/kg.

Doses:
Dose Ranging Study- 1000, 2000, 3000, 4000 and 5000 mg/kg
Main Study- 5000 mg/kg
No. of animals per sex per dose:
Dose Ranging Study-2 males and 2 females per dose level
Main Study- 5 male and 5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed frequently on the day of dosing and once daily for 14 days following dosing. The rats were weighed immediately prior to dosing, 7 days after dosing (main study only) and at sacrifice at the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
There were no deaths and no abnormalities were detected at necropsy.
Clinical signs:
Clinical signs noted 1/2 h-4 h after dosing, included piloerection and reduced activity.
Body weight:
Body weight gains were acceptable with the exception of one male which showed a lower weight gain than expected.
Gross pathology:
No abnormalities were detected at necropsy.
Other findings:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median oral lethal dose (LD50) of T-4388 in rats was greater than 5000 mg/kg. Hence, the test material is not classified as per EU classification.
Executive summary:

The acute oral toxicity potential of a test material, T-4388, a colorless liquid, lot 6, was investigated in rats. Fifteen male and fifteen female nulliparous and non-pregnant rats of the Sprague Dawley strain were used. They were 6-8 weeks old and weighed 151-210 g at dosing in the main test.

The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum of 6 animals per cage for the dose ranging study and 5 animals per cage for the main study. The rats were fed Expanded Rat and Mouse Maintenance Diet, except for 19-20 h before dosing and for 1.5-2.5 h post dosing. Tap water was available ad libitum throughout the study.

Mean environmental maximum and minimum temperatures were 21ºC and 19 ºC and mean relative humidity was 40%. Rats were allowed an acclimatization period of at least 9 days before test commencement.

The vehicle used for the dosing solution was corn oil. The test material was administered orally in single dose by means of a gavage at a constant dose volume of 10 ml/kg. The rats were observed frequently on the day of dosing and once daily for 14 days following dosing. They were weighed immediately prior to dosing, 7 days after dosing (main study only) and at sacrifice at the end of the observation period. At the end of the observation period and sacrifice by carbon dioxide asphyxiation, each animal was subjected to necropsy.

A dose ranging study in pairs of rats indicated that the oral LD50 value was greater than 5000 mg/kg. A main study dose level of 5000 mg/kg was selected accordingly. No further testing at other dose levels was necessary.

In the main study, no deaths occurred after administration of T-4388 at a dose level of 5000 mg/kg. Clinical signs noted ½ h-4 h after dosing, included piloerection and reduced activity. No abnormalities were detected at necropsy.

The median oral lethal dose (LD50) of T-4388 was greater than 5000 mg/kg. Hence, the test material is not classified as per EU classification.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
good

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:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The data quality from this study is considered acceptable. The report included documentation for methods and results. This study reaches Klimisch Level 2.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 12 weeks
- Weight at study initiation: not specified in the report
- Fasting period before study: not specified in the report
- Housing: standard conditions
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1-week prior to testing


ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard conditions
- Humidity (%): standard conditions
- Air changes (per hr): standard conditions
- Photoperiod (hrs dark / hrs light): 12 hours light : 12 hours dark
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The vapor atmosphere was generated by metering DPMA into a J tube into which heated air (100°C) was directed. The resulting vapor was diluted to the desired concentration with room temperature air

TEST ATMOSPHERE
- Brief description of analytical method used: not analysed
- Samples taken from breathing zone: not applicable

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not applicable
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not applicable
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
5.7 mg/liter or 5,700 mg/cubic meter (734 ppm).
No. of animals per sex per dose:
6 males
Control animals:
yes
Details on study design:
- Six male rats were exposed to 0 and 5.7 mg/liter DPMA for 4 hours in 112-liter, stainless steel and glass whole-body inhalation chambers. The test atmosphere was not analyzed. Rather, the exposure concentration was calculated (as nominal) from the amount of DMPA used divided, by the air flow. Rats were observed for mortality and signs of toxicity over the course of exposure and the 2-week observation period. After 24 hours, one control and one DPMA-exposed rat were sacrificed and subjected to gross necropsy. After 14 days of observation, the remaining animals were sacrificed and a necropsy was performed
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed and weighed prior to exposure and at intervals post-exposure for 2 weeks.
- Necropsy of survivors performed: yes
Sex:
male
Dose descriptor:
LC50
Effect level:
> 5.7 mg/L air
Exp. duration:
4 h
Remarks on result:
other: equivalent to approximately 734 ppm)
Mortality:
No mortality observed during the study period.
Clinical signs:
other: None of the exposed rats exhibited any adverse signs during or after the exposure period
Body weight:
All rats showed body weight gain comparable to control rats
Gross pathology:
No treatment related lesions were observed in any of the animals at necropsy.
Table 1: Concentrations and results of mortality
 Nominal conc.  Analytical conc.  No. dead/total males  No. dead/total females Total no. dead/total 
 0 mg/l  0/6  0/6
 5.7 mg/l  0/6  -  0/6
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The DPMA 4-hour inhalation LC50 for males is greater than 5.7 mg/l (or > 5,700 mg/m3). No deaths occurred in 6 males at this exposure level so the actual LC50 may be considerably higher than this value. Actual concentrations were not measured and the calculated vapor concentration is greater than the theoretical maximum. However, no condensation was reported on the chamber walls so a supersaturated condition may have existed.
Executive summary:

Dipropylene Glycol Monomethyl Ether Acetate (Dowester A50B/DPC-Herb Jackson 1710) was evaluated for acute inhalation toxicity on male Fischer 344 rats to a calculated vapour concentration of 5.7 mg/l (equivalent to 734 ppm) and the exposure did not result in any adverse effects during or after the exposure period. All exposed rats showed body weight gain comparable to control rats and no treatment related lesions were observed in any of the animals at necropsy.

Under the conditions of the study, the DPMA 4-hour inhalation LC50 for males is greater than 5.7 mg/l (or > 5,700 mg/m3).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
good

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:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted in accordance with GLP and guidelines and sufficient data is available for the interpretation of study results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River ( UK )
- Age at study initiation: 8-10 weeks
- Weight at study initiation:211-297g
- Fasting period before study: not specified
- Housing: The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum number of 5 animals per cage
- Diet ( ad libitum): Expanded rat and mouse maintenance diet supplied by special diet services
- Water ( ad libitum): Tap water ad libitum
- Acclimation period: 9 days


ENVIRONMENTAL CONDITIONS
- Temperature °C: Mean environmental maximum and minimum temperatures were 21°C and 19°C
- Humidity (%): Mean relative humidity 40 %
- Photoperiod (hrs dark / hrs light): 12 hrs dark /12 hrs light


Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure:clipped intact skin of the back
- % coverage: 10 % of body surface
- Type of wrap if used: Strip of non-irritating material


REMOVAL OF TEST SUBSTANCE
-After the contact period (24 hours) dressing was removed and the skin wiped with a water dampened tissue to remove excess test material


Duration of exposure:
24 hrs
Doses:
500, 1000, 1500, 2000 mg/kg for range finding study
2000 mg/kg for main study
No. of animals per sex per dose:
2 males and 2 females/dose level for range finding study
5 males and 5 females for main study
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed frequently on the day of dosing and for 14 days following dosing. Rats were weighed immediately prior to dosing, 7 days after dosing and at the end of 14 day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and Necropsy findings
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived.
2000 mg/kg (Males ) - 0/5
2000 mg/kg (Females ) - 0/5
Clinical signs:
There were no deaths and no clinical signs were noted.
2000 mg/kg (Males ) - No clinical signs observed
2000 mg/kg (Females )
Body weight:
All animals showed body weight gain over the 14 day observation period.
Gross pathology:
No abnormalities were detected at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study the median lethal dose (LD50) of T-4388 in rats is greater than 2000 mg/kg.
Executive summary:

The acute dermal toxicity potential of test material, T-4388 (Colorless liquid) was investigated in 5 males and 5 females Sprague-Dawley rats. Doses selected for range finding study were 500, 1000, 1500, 2000 mg/kg and 2000 mg/kg for the main study

Rats were received from Charles River (UK) and all received rats were kept for 9 days acclimatization period. Animal rooms were maintained at a temperature 19-21°C and relative humidity of 40 % with 12 hrs dark /12 hrs light photoperiod. The rats were fed expanded rat and mouse maintenance diet supplied by special diet services with ad libitum tap water. The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum number of 5 animals.

Rats were prepared by clipping the backs free of hair, approximately 24 hours before application of test material. The test material, as supplied was applied evenly onto gauze dressing which was applied to shaved back of each rat. Up to at least 10 % of the body surface was in contact with the test material. The trunk of the rat then encircled with as strip of non-irritating tape. After the contact period (24 hours) dressing was removed and the skin wiped with a water dampened tissue to remove excess test material. Rats were observed frequently on the day of dosing and for 14 days following dosing and weighed immediately prior to dosing, 7 days after dosing and at the end of 14 day observation period. At the end of observation period all the animals were sacrificed by carbon dioxide asphyxiation.                

All animals showed body weight gain over the 14 day observation period. There were no deaths and no clinical signs were noted at 2000 mg/kg dose level. No abnormalities were detected at necropsy. Based on the results of this study the median lethal dose (LD50) of T-4388 in rats is greater than 2000 mg/kg.According to EU this test material is not classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
good

Additional information

Acute Oral toxicity:

There are 2 acute oral toxicity studies available in rats. Both give an LD50 value of >5000 mg/kg bw.

Acute Dermal toxicity:

There are 2 acute dermal toxicity studies available, one in rats, and one in rabbits. The LD50 in rats was greater tahn 2000 mg/kg bw, and in rabbits it was greater than 5000 mg/kg bw.

Acute inhalation toxicity:

In a study performed to a protocol similar to the standard guideline, the highest dose tested of 734 ppm (5.7 mg/L) was non-toxic and this was the highest attainable vapour concentration. As such the LC 50 is greater than 5.7 mg/L.


Justification for selection of acute toxicity – oral endpoint
this study was selected as the key study as it is reliable without restriction (Klimisch rating 1)

Justification for selection of acute toxicity – inhalation endpoint
this study was identified as key for this toxicity endpoint because of the methods followed (which were comprehensively documented in the report). While the report did not include GLP and Quality Assurance statements and did not specifically reference OECD Protocol 403: "Acute Inhalation Toxicity," the standards specified in this guidance were generally followed. Specifically, the numbers and type of test animals used and their husbandry conditions followed guidance. Test material characterization was adequate except for the use of only nominal concentrations (acceptable for an acute test). The dose level tested (in this limit test) satisfied the appropriate OECD upper limit, the length of the observation period (14 days) was sufficient, and the toxicity endpoints monitored were typical for this type assay and adequately recorded.

Justification for selection of acute toxicity – dermal endpoint
this study was selected as the key study as it is reliable without restriction (Klimisch rating 1)

Justification for classification or non-classification

The oral and dermal LD50 values are greater than 2000 mg/kg. The inhalation LC50 was greater than 734 ppm the highest attainable concentration. According to EU criteria no classification for acute toxicity for any route of exposure is required for dipropylene glycol methyl ether acetate.