Potassium hexadecyl hydrogen phosphate

Endpoint summary

Description of key information

The substance was found to cause severe eye damage (irreversible) in rabbits in an OECD guideline study. Results of a skin irritation study according to OECD 404 with the test substance in rabbits showed that the substance is not a skin irritant. 

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:

key study

Study period:

2005-03-08 until 2005-03-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

adopted 2004-04-29

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 2002-04-24

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353, 88353 kißlegg
- Weight at study initiation: 2.0-2.4 kg
- Housing: in fully air-conditioned rooms in separate cages arranged in in battery
- Diet: ssniff K-H (V2333), ad libitum and hay (approx 15 g daily)
- Water: tap water in plastic bottles, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Humidity: 50 ± 20 %
- Photoperiod: 12 hours light / dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

abraded

Vehicle:

other: sesame oil was used as a vehicle for pasting the test item

Controls:

not required

Amount / concentration applied:

Single dose of 0.5 g of the test substance (pasted with 0.3 mL sesame oil)

Duration of treatment / exposure:

4 hours

Observation period:

60 minutes and 24, 48, 72 hours after removal of the patches.

Number of animals:

3 animals

Details on study design:

TEST SITE
The test item was evenly distributed over the whole surface of a 2.5 x 2.5 cellulose patch on a piece of surgical plaster (specially produced by Beiersdorf Aktiengesellschaft). The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.

REMOVAL OF TEST SUBSTANCE
After the exposure period all remainings of the test item were carefully removed from the skin with warm tap water.

SCORING SYSTEM:
Erythema, eschar formation and edema were evaluated numerically according to the score of DRAIZE. All other changes of the skin were recorded as well.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of irritations were observed during the study

An initial test was performed using one animal. As no corrosive effects were observed in the initial test a confirmatory test with two further animals was conducted.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study the test substance is not irritating to skin.

Executive summary:

An initial test was performed using one animal. As no corrosive effects were observed in the initial test a confirmatory test with two further animals was conducted. Altogether, 3 female New Zealand White rabbits were tested for skin irritation according to OECD Guideline 404 and EU Method B.4 with 0.5 g of the test substance moistened in 0.3 mL sesame oil per animal for an exposure period of 4 hours. No signs of irritation were observed occurred during the whole observation period. Based on the system of evaluation defined by EC, the following overall mean scores for dermal irritation after 24, 48 and 72 hours were calculated: Erythema and eschar formation - 0 and Edema formation - 0. It can be concluded, based on the results of this study that the test substance is not imtating to skin of rabbits.

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:

2005-03-22 until 2005-04-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kißlegg
- Weight at study initiation: 3.44 kg
- Housing: in fully air-conditioned rooms in separate cages arranged in a battery
- Diet: ssniff K-H (V2333) ad libitum and hay (approximately 15 g daily)
- Water: tap water in plastic bottles, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Humidity: 50 ± 20 %
- Photoperiod: 12 hours light / dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Single dose of 100 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48 and 72 hours after administration of the Test item. Since effects were still present in the eye after 72 hours, further estimations were carried out after 7 and 14 days.

Number of animals or in vitro replicates:

1 animal

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: isotonic saline
- Time after start of exposure: 24 hours after administration

SCORING SYSTEM: As indicated in the guideline

TOOL USED TO ASSESS SCORE: fluorescein-sodium solution

- An initial test was performed using one animal. As the test item showed potential risk of serious damage to eyes only one animal was used in the study
- About 24 hours before the start of the study both eyes of the animal was examined under UV light for corneal lesions after instillation of one drop of a 0.01 % fluorescein-sodium solution. Only animals without ocular abnormalities were used for the study.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.66

Max. score:

3

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not fully reversible within: 14 days

The conjunctiva of the animal showed 1 hour up to the end of the study (14 days after administration) some diffuse beefy red color and obvious swelling with partial eversion of lids up to swelling with about half closed lids. The cornea showed scattered areas from day 2 up to the end of the study; up to 50 % or slightly more of the cornea was affected. In addition to these observations, the animal showed also colorless serious eye discharge one up to 24 hours after administration. Thereafter up to the end of the study the animal showed white mucous eye discharge. The animal showed additionally vascularization of the cornea from day 8 (slight) up to day 15 (extreme) of the study which indicates irreversible effects. On day 15 the animal was therefore killed for animal welfare reasons.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Testing of the test substance for primary eye irritation in the rabbit showed that the test item caused severe ocular lesions (risk of serious damage to eyes).

Executive summary:

In an eye irritation study according to OECD guideline 405, an amount of 100 mg of the test substance was administered once to the conjunctival sack of the left eye of one female New Zealand White rabbit. The treated eye was washed out 24 hours after the administration of the test item. The untreated eye served as a control.

The test item caused irritating effects in the eye of the animal up to 14 days (end of study) after administration. Extreme cornea vascularization was observed on day 15 indicating irreversible effects and the animal had to be killed for animal welfare reasons. No clinical signs of systemic toxicity were observed.

Summarizing, testing for primary eye irritation in the rabbit showed that the test substance caused severe ocular lesions (risk of serious damage to eyes).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

An initial test was performed using one animal. As no corrosive effects were observed in the initial test a confirmatory test with two further animals was conducted. Altogether, 3 female New Zealand White rabbits were tested for skin irritation according to OECD Guideline 404 and EU Method B.4 with 0.5 g of the test substance moistened in sesame oil per animal for an exposure period of 4 hours. No signs of irritation were observed during the whole observation period. Based on the system of evaluation defined by EC, the following overall mean scores for dermal irritation after 24, 48 and 72 hours were calculated: Erythema and eschar formation - 0 and Edema formation - 0. It can be concluded, based on the results of this study that the test substance is not irritating to skin of rabbits. The results of the animal studies were supported by the results of a repeated insult (occlusive) patch test procedure in human subjects (see section 7.10.4) with 6 % of the test substance. The study showed that the test substance does not induce irritant or allergic contact dermatitis in human subjects.

Eye irritation

In an eye irritation study according to OECD guideline 405, an amount of 100 mg of the test substance was administered once to the conjunctival sack of the left eye of one female New Zealand White rabbit. The treated eye was washed out 24 hours after the administration of the test item. The untreated eye served as a control.The test item caused irritating effects in the eye of the animal up to 14 days (end of study) after administration. Extreme cornea vascularization was observed on day 15 indicating irreversible effects and the animal had to be killed for animal welfare reasons. No clinical signs of systemic toxicity were observed.

Summarizing, testing for primary eye irritation in the rabbit showed that the test substance caused severe ocular lesions (risk of serious damage to eyes).

Results of the supporting study were in line with the results of the key study. When the study results are analysed according to the CLP criteria lead at least to eye irritation Cat. 2. As the study terminated 72 hours after test substance application, reversibility of the results after 21 days is questionable. Therefore no classification and labelling for eye irritation Cat. 1 could be determined. It was shown that the test substance in both concentrations (30 % and 100%) results in conjunctivae redness in a score of >= 2 and cornea opacity of >= 1 were observed in 2 out of 3 animals (when calculated as mean scores after 24, 48 and 72 hours for each of the two animals). When following classification and labelling criteria of Regulation (EC) No 1272/2008 (CLP), and assuming reversible effects (although this is not evident), the test substance in concentrations of 30 % and 100 % (but not with 10 % of the test substance, which is similar to the concentration in the product) should be classified and labelled for eye irritation cat. 2.

Justification for classification or non-classification

Based on the results obtained, potassium hexadecyl hydrogen phosphate was classified and labelled for eye damage Cat.1 H318 according to Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521. The substance was not subjected to classification and labelling for skin irritation according to Regulation (EC) No 1272/2008.