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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Start: 26 October 1998 End: 5 November 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
O,O-tert-butyl isopropyl monoperoxycarbonate
EC Number:
219-143-7
EC Name:
O,O-tert-butyl isopropyl monoperoxycarbonate
Cas Number:
2372-21-6
Molecular formula:
C8H16O4
IUPAC Name:
tert-butoxy propan-2-yl carbonate
additive 1
Reference substance name:
Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction, hydrogenated
EC Number:
297-629-8
EC Name:
Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction, hydrogenated
Cas Number:
93685-81-5
Molecular formula:
not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)
IUPAC Name:
isododecane
Test material form:
liquid
Details on test material:
Trigonox BPIC-C75
Specific details on test material used for the study:
The specific details of the test material used for this study were as follows:
Akzo Nobel Trade Name: Trigonox BPIC-C75
Chemical Name: Tert-butylperoxy isopropyl carbonate, 75% solution in aromatic free mineral spirit
CAS-No.: 2372-21-6
Batch: 0419804130350
Test substance storage: In refrigerator in the dark
Do not heat test substance
Stability under storage conditions: Not indicated
Expiry date: 01 October 1999 (allocated by NOTOX, 1 year after receipt of the test substance}
Density: 900-910 kg/ms (20°C)
The test substance was not heated above the temperature of 70°C.
Preparation: The test substance was instilled undiluted as delivered by the sponsor.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species: Albino rabbit, New Zealand White (SPF-Quality). Recognised by international guidelines as the recommended test system {e.g. EC, OECD}
Source: Broekman Institute, Someren, The Netherlands.
Number of animals: 3 Animals of either sex.
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were less than 3.5 kg.
Identification: Ear tag.

ANIMAL HUSBANDRY
Conditions:
Air-conditioned room with approximately 15 air changes per hour and the environment controlled with optimal conditions considered as being a temperature of 21°C and a relative humidity of 50%. Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity. Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

Accommodation:
Individually housed in labelled cages with perforated floors (Scanbur, Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet:
Standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day. Certificates of analysis were examined and retained in the NOTOX archives.
In addition, hay (BMI, Helmond, the Netherlands) was provided once a week.

Water:
Free access to tap-water diluted with decalcified water. Certificates of
quarterly analysis were examined and retained in the NOTOX archives.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL of test substance
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
As marked effects were considered possible (based on results of the skin irritation study, NOTOX project 245205 and on the information provided by the sponsor) this study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of eye irritation observed in the first animal.
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.
On test day 1, 0.1 ml of the test substance was instilled in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.

OBSERVATIONS
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation).
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and/or 7 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: also 1 hour
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: also 1 hour
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: also 1 hour
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: also 1 hour
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: also 1 hour
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: also 1 hour
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Score given for eyelids
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Score given for Eyelids and Nictitating membrane
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Score given for Eyelids
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
other: 1 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Score given for Eyelids
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Score based on Eyelids and Nictitating membrane
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Score based on Eyelids
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
other: 1 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Score based on Eyelids
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Score based on Eyelids and Nictitating membrane
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Score based on Nictitating membrane
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: score given for Eyelids
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 1 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Score based on Eyelids
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 1 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Score based on Eyelids
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
other: Discharge
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
other: Discharge
Basis:
animal #2
Time point:
other: 1 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 h
Irritation parameter:
other: Discharge
Basis:
animal #3
Time point:
other: 1 h
Score:
0
Max. score:
3
Irritant / corrosive response data:
Irritation
Instillation of 0.1 ml of TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT into one eye of each of three rabbits resulted in
irr itat ion of the conjunctivae, wh ich consisted of redness, chemosis and discharge. The irr itat ion had completely resolved w ithin 72 hours in two animals and within 7 days in the other animal.
No iridic irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.
Corrosion
There was no evidence of ocular-corrosion.
Other effects:
Colouration
No staining of peri-ocular tissues by the test substance was observed.
Toxicity/Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results and according to the EC criteria for classificat ion and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75%
SOLUTION IN AROMATIC FREE MINERAL SPIRIT does not have to be classified and has no obligatory labelling requirement for eye irritation.
Executive summary:

Acute eye irritation/corrosion study with TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT in the rabbit.

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B.5, "Acute Toxicity - Eye irritation" and OECD No.405, "Acute Eye Irritation/Corrosion".

Single samples of 0.1 ml of TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and/or 7 days after instillation.

Instillation of TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT resulted in irritation of. the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in two animals and within 7 days in the other animal.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT does not have to be classified and has no obligatory labelling requirement for eye irritation.