[2-(2-methoxymethylethoxy)methylethoxy]propanol

Endpoint summary

Description of key information

GLP-studies according to EPA/OPP guidelines for skin and eye irritation are available for tripropylene glycol methyl ether. These are supported by non-GLP studies equivalent or similar to OECD guidelines 404 and 405.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted prior to GLP and guidelines. The report contains sufficient amount of data for the interpretation of the results. Non-GLP studyequivalent to OECD guideline 404. Quality Check: This study was performed prior to establishment of GLPs or publication of protocol guidelines. The report included very limited documentation for methods and results but the performing institution, Carnegie Mellon, was/is highly regarded. As typical for a study this old, the report did not provide sufficient documentation that elements of OECD Protocol 404: "Acute Dermal Irritation/Corrosion" were followed, although the numbers and type of test animals used (but not their husbandry conditions) were as recommended in the guidance. Remarkably, the length of time that test material was held in contact with the skin was not defined. Test material characterization was not addressed other than to identify batch numbers, amount received, and receipt dates. While the length of the observation period was not explicitly stated it is presumed to have been the typical 14 days or until all signs of irritation had regressed; the toxicity endpoints monitored were typical for this type assay and adequately recorded.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

open

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.010ml

Duration of treatment / exposure:

24 hour(s)

Observation period:

14 days

Number of animals:

5

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 hours to 14 days

Score:

1

Max. score:

10

Reversibility:

other: no irritation effects observed

Irritant / corrosive response data:

no injury is judged to be a grade 1.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Tripropylene glycol methyl ether (TPM) does not appear to be irritating to the skin of rabbits under the conditions of this test.
Classification: not irritating

Executive summary:

Tripropylene glycol methyl ether (TPM) was tested for skin irritation in albino rabbits. 3 to 5 old male rabbits were used. TPM was applied to the intact clipped skin of the belly of 5 albino rabbits for an unspecified period of time. The application site was not covered and, presumably, subjects were restrained to prevent grooming and consequent ingestion (subjects were restrained in the dermal LD50 test by the same institution, described above, on this same batch of test material). Irritation was scored on a scale of 1 to 10, based on moderate or marked capillary injection, erythema, edema or necrosis within 24 hours. While the length of the observation period was not explicitly stated it is presumed to have been the typical 14 days or until all signs of irritation had regressed; the toxicity endpoints monitored were typical for this type assay and adequately recorded. No evident injury is judged to be a Grade 1.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to EPA/OPP guideline and in accordance with GLP

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Principles of method if other than guideline:

Guideline study

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Clerco Research Farm, Cincinnati, OH.
- Age at study initiation: Young adult
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature: 67±5 Deg. F
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): One-tenth (0.1) millitier/eye

Duration of treatment / exposure:

0.1 ml of material was placed in the right eye .
The treated eyes of 6 rabbits were unwashed.
The treated eyes of 3 rabbits were washed for 1 minute with lukewarm tap water at a rate of approximately 1 liter per minute beginning approximately 30 seconds after installation of the test article.

Observation period (in vivo):

1, 24, and 48 hours and 72 hours.

Number of animals or in vitro replicates:

Unwashed eye group-6 animals
Washed eye group- 3 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing : The treated eyes of 3 rabbits were washed for 1 minute with lukewarm tap water at a rate of approximately 1 liter per minute beginning approximately 30 seconds after installation of the test article.

- Time after start of exposure: The right eye of each animal was examined for ocular irritation and lesions at 1 hour
(± 15 minutes), and at 24, 48, and 72 hours (± 2 hours at each interval).


SCORING SYSTEM: Draize Score

TOOL USED TO ASSESS SCORE: A pocket flashlight without magnification was used at all evaluation intervals, and a 2% sodium fluorescein solution in deionized water was used at all evaluations except for those done at 1 hour after instillation.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over 6 animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Remarks on result:

other: unwashed eye group

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over 6 animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Remarks on result:

other: washed eye group

Irritation parameter:

iris score

Basis:

mean

Remarks:

over 6 animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Remarks on result:

other: unwashed eye group

Irritation parameter:

iris score

Basis:

mean

Remarks:

over 6 animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Remarks on result:

other: washed eye group

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

over 6 animals

Time point:

other: 24, 48 and 72 hours

Score:

0.4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: unwashed eye group

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

over 6 animals

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: washed eye group

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

over 6 animals

Time point:

other: 24, 48 and 72 hours

Score:

0.6

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: unwashed eye group

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

over 6 animals

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: washed eye group

Other effects:

None

None

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the annex VI of the council directive 67/548 EEC (amended by directive 83/467 EEC) the average scores over all animals for cornea opacity, iris lesions, conjunctivae and chemosis were 0, 0, 0.4 and 0.6, respectively at 24, 48 and 72 hours. According to EEC criteria no classification for eye irritancy is required.

Executive summary:

The test article, A273956, was evaluated for primary eye irritation after instillation in the right eyes of 9 rabbits.

This study was designed to comply with the procedure described in EPA/OPP Guidelines, 1982.

The eyes of 3 of these 9 rabbits were washed with lukewarm tap water after instillation. The treated eyes of all animals (washed and Unwashed) were evaluated at 1, 24, 48, and 72 hours after installation.

No mortalities or abnormal clinical signs were observed during the study. Blistering of the conjunctivae was noted for all the unwashed and washed group animals at the one hour evaluation, which was fully reversible before 72 hours.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two skin irritation studies are available for tripropylene glycol methyl ether. Both studies are considered to be reliable with restrictions (Klimisch 2). In the identified key study (Dow, 1977) with unoccluded dermal application of tripropylene glycol methyl ether to rabbits produced no irritation, the overall mean irritation score (24 hours to 14 days) was 1 out of a maximum score of 10.

In the second key study (Lyondell, 1984), using impermeable occlusion for 24 hours, skin irritation was observed. All effects were reversible within 14 days. This study using impermeable occlusion is likely overestimating the irritancy of the test material and current guidelines are recommending semi-occlusive dressing. Therefore, on the basis of the earlier Dow, 1977 study, tripropylene glycol methyl ether is not considered to be a skin irritant under standard conditions.

Overall, three eye irritation studies are available for tripropylene glycol methyl ether. In the identified key study (Arco, 1984), only slight and fully reversible effects were observed after administration of tripropylene glycol methyl ether to rabbits eyes. The mean corneal and iris scores (for 6 rabbits) was 0 across 24, 48 and 72 hours in both the washed and unwashed eyes. The mean conjunctival scores were 0.4 (unwashed eye group) and 0.3 (washed eye group), while the mean chemosis scores were 0.6 (unwashed eye group) and 0.3 (washed eye group), respectively. There were no cumulative effects and these effects were fully reversible within 48 -72 hours. In the supporting study (Dow, 1977 and Dow, 1953), fluorescein staining revealed no corneal injury.

Justification for selection of skin irritation / corrosion endpoint:
Although the study was conducted prior to GLP and guidelines, the report contains sufficient information to permit a meaningful evaluation of study results.

Justification for selection of eye irritation endpoint:
The study was conducted according to EPA/OPP guideline and in accordance with GLP.

Justification for classification or non-classification

Based on EU criteria, no classification for skin and eye irritation is required for tripropylene glycol methyl ether.

Eye irritation: according to the annex VI of the council directive 67/548 EEC (amended by directive 83/467 EEC) the average scores over all animals for cornea opacity, iris lesions, conjunctivae and chemosis were 0, 0, 0.4 and 0.6, respectively at 24, 48 and 72 hours. According to EEC criteria no classification for eye irritancy is required.