Propan-1-ol

Endpoint summary

Description of key information

Negative results were obtained in three different tests (Guinea pig maximization test, mouse ear swelling test and closed patch test) regarded to be acceptable for assessment.
The results are supported by negative findings in a human insult patch test performed with 50 subjects. In contrast in another patch test a positive reaction was observed in one human which was primarily exposed to isopropylalcohol

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Principles of method if other than guideline:

Closed patch test

GLP compliance:

no

Type of study:

patch test

Specific details on test material used for the study:

Analytical purity: > 99.8%

Species:

other: no data

Strain:

not specified

Sex:

not specified

Route:

epicutaneous, open

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

No. of animals per dose:

no data

Positive control substance(s):

not specified

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Method: other

GLP compliance:

no

Type of study:

mouse ear swelling test

Justification for non-LLNA method:

The LLNA method was not available yet by the time the study was conducted.

Specific details on test material used for the study:

Analytical purity: > 98 %

Species:

mouse

Strain:

CF-1

Sex:

female

Details on test animals and environmental conditions:

- Age at study initiation: 6-8 weeks
- Housing: 5/cage
- Diet: ad libitum, (Purina Rodent Laboratory Chow 5001)
- Water: ad libitum
- Aclimation: 7 days (during this period, any animal with red or swollen ear disqualified and was removed from the study)

Route:

intradermal and epicutaneous

Vehicle:

unchanged (no vehicle)

Concentration / amount:

Induction: 100%
Challenge: 100%

Route:

epicutaneous, open

Vehicle:

unchanged (no vehicle)

Concentration / amount:

Induction: 100%
Challenge: 100%

No. of animals per dose:

Test groups: 10
Irritation control: 5

Details on study design:

PRELIMINARY RANGE FINDING TEST

- Number of animals: 2/concentration
- Induction: procedure as described in main study whereby four concentrations were used for induction; no further information
- Challenge: each group was challenged at a different concentration; no further details given
- Evaluation: 24 h after challenge
Results: Concentrations utilized in the main study was the highest with minimal iiritation or non-iiritating to the stomach (for induction) and nonirritating to the ear (for challenge)

MAIN STUDY

IRRITATION CONTROL ANIMALS
INDUCTION EXPOSURE:
- Site of application: Abdomen
- Shaved: yes, before application on Day 0
- FCA (Freund's Complete Adjuvant) pretreatment: Yes, injected intradermally 2x á 0.05 ml after which the abdominal skin was then tape stripped.
- Volume: it is unclear from reporting if control animals were induced with a control substance or not, since test substance was applied undiluted (unchanged)
- Repeation: Yes, tape stripping and topical induction applications were repeated for additional 3 consecutive days

CHALLENGE
- Time schedule: 7 days after induction
- Area of application: left ear, (test substance); right ear (treatment unclear; untreated or if treated what solvent was employed)
- Volume applied: 20 µl
- Concentration: undiluted (100%)
- Evaluation: 24h and 48h after challenge
- Anesthesia: Yes, ether before measurement

TEST GROUP
INDUCTION EXPOSURE:
- Site of application: Abdomen
- Shaved: yes, before application on Day 0
- FCA (Freund's Complete Adjuvant) pretreatment: Yes, injected intradermally 2x á 0.05 ml after which the abdominal skin was then tape stripped.
- Volume (Test substance): 100µl applied topically to the center of the shaved region. Area dried with electric dryer
- Concentration: undiluted (100%)
- Repeation: Yes, tape stripping and topical induction applications were repeated for additional 3 consecutive days

CHALLENGE
- Time schedule: 7 days after induction
- Area of application: left ear, (test substance); right ear (treatment unclear; untreated or if treated what solvent was employed)
- Volume applied: 20 µl
- Concentration: undiluted (100%)
- Evaluation: 24h and 48h after challenge
- Anesthesia: Yes, ether before measurement

Positive control substance(s):

yes

Remarks:

Ethylene diamine, dinitrochlorobenzene and p-phenylenediamine

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Induction 100%; challenge 100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no data

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction 100%; challenge 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Induction 100%; challenge 100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no data

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction 100%; challenge 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.

Reference 3

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

(no pretreatment of skin with SDS before topical induction, time of evaluation after challenge not given)

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The LLNA method was not available yet by the time the study was conducted.

Specific details on test material used for the study:

Analytical purity: > 99.8%

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- not reported

Route:

other: intradermal and epicutaneous occlusive

Vehicle:

no data

Concentration / amount:

INDUCTION (intradermal and topical): 100%
CHALLENGE: 100%

Route:

epicutaneous, occlusive

Vehicle:

no data

Concentration / amount:

INDUCTION (intradermal and topical): 100%
CHALLENGE: 100%

No. of animals per dose:

Test group: 15
control group: 6

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
INTRADERMAL INDUCTION
- No. of exposures: 2
- Test groups: a). substance undiluted, b).FCA, c). Test substance in FCA
- Control group: a). vehicle undiluted, b).FCA, c). vehicle in FCA (unclear what was used as vehicle since test substance was applied at a concentration of 100%)
- Site: no data
- Frequency of applications: no data
- Concentrations: 100%

TOPICAL INDUCTION (occlusive)
- Day(s) after intradermal induction: 7 days after
- No. of exposures: 1
- Test groups: undiluted test substance applied to skin
- Control group: undiluted vehicle applied to skin (unclear what was used as vehicle since test substance was applied at a concentration of 100%)
- Site: same site as intradermal induction
- Duration: 48h
- Concentrations: 100%

B. CHALLENGE EXPOSURE (topical occlusive)
- Day(s) after topical induction: 14 d
- Day of challenge: 21 days after intradermal induction
- No. of exposures: 1
- Exposure period: 24h
- Test groups: undiluted test substance applied to skin
- Control group: undiluted vehicle applied to skin (unclear what was used as vehicle since test substance was applied at a concentration of 100%)
- Site: naive skin
- washing of skin after application: no data
- Concentrations: 100%
- Evaluation (hr after challenge): no data

OTHER:
if neccessary a rechallenge was planned 7 day after challenge

Positive control substance(s):

yes

Remarks:

Dinitrochlorobenzene (intra dermal induction: 0.1%; topical induction; 0.1%; challenge; 0.1%), vehicle; propylene glycol

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

15

Clinical observations:

no data

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: no data.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

6

Clinical observations:

no data

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 6.0. Clinical observations: no data.

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1% in propylene glycol

No. with + reactions:

15

Total no. in group:

15

Clinical observations:

no data

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1% in propylene glycol. No with. + reactions: 15.0. Total no. in groups: 15.0. Clinical observations: no data.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

NON HUMAN DATA

In a dermal sensitization study (Gad et al. 1986) with propan-1-ol (> 99.8%), Hartley Guinea Pigs (15/dose, no data on sex) were tested using the Guinea Pig Maximization Test. 6 animals were used in the control group. Undiluted propan-1-ol (100%) was employed for the intra-dermal induction phase. Topical induction (TI) was performed occlusively with undiluted propan-1-ol (7 days post intra-dermal induction). 14 days after TI, naïve skin was challenged with undiluted propan-1-ol. Dinitrochlorobenzene in propylene glycol was employed as the positive control substance (intra-dermal induction: 0.1%, topical induction: 0.1%, challenge: 0.1%). No positive reaction was observed in the test and negative control animals. The positive control caused the appropriate response (15/15 positive reactions). In this study, propan-1-ol is not a dermal sensitizer.

In support of the results of GPMT assay, are the results of a Mouse Ear Swelling Test (MEST) reported by Gad et al. (1986). Intra-dermal induction was performed with undiluted propan-1-ol on 10 female CF-1 mice. The animals were challenged with undiluted propan-1-ol 7 days following induction. No positive reaction was observed at either measurement time (24 and 48 hours after challenge) in the test group.

Also, negative results were obtained in a closed patch test with guinea pigs (Gad et al., 1986).

HUMAN DATA

A positive patch test reaction to propan-1-ol (test concentration: undiluted or 50 %) was elicited in a woman sensitive to 2-propanol and 1-butanol but not to primary alcohols with less than 3 C atoms and other substances. The woman worked in the laboratories of a cosmetic company and she was primarily exposed to commercial isopropyl alcohol (Ludwig and Hausen 1977).

Fifty subjects were patch tested with nine 24-hour applications of 0.2 ml substance over a three week period and challenge patching 10 to 14 days later. In all subjects the response was negative (Gad et al. 1986).

Among 145 patients patch tested with i.a. propan-1-ol, only one nurse was detected with a possible allergy to 1-propanol (Kreipe et al., 2020). The clinical relevance of the positive patch test result was controlled by repetitive open application tests (ROATs), which were performed two times daily over 7 days. Although the first ROAT was positive, a second one was not able to confirm the finding.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In reliable animal and human tests no sensitising potential was observed. There is only one case where positive reactions have been shown after patch testing to propan-1-ol and other substances. Thus, according to Regulation (EC) No. 1272/2008 there is no need for classifcation for skin sensitisation.