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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published test report from Nagoya Medical Journal Evaluated data from a reliable secondary source (US-CPSC, 1999; ACGIH, 2005).

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1975
Report date:
1975
Reference Type:
secondary source
Title:
Unnamed
Year:
2000
Reference Type:
secondary source
Title:
Unnamed
Year:
2005
Report date:
2005
Reference Type:
secondary source
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Principles of method if other than guideline:
Rabbits and rats were dosed daily for 20 days with 15%, 20%, or 30% queous solutions of THPC.
Treated animals were continuosly placed under observation even therafter the treatment was discontinued. All animals wer sacrificed after
completion of the experiments and their hematoxylin-eosin stained skin specimens were histological examined.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrakis(hydroxymethyl)phosphonium chloride
EC Number:
204-707-7
EC Name:
Tetrakis(hydroxymethyl)phosphonium chloride
Cas Number:
124-64-1
Molecular formula:
C4H12O4P.Cl
IUPAC Name:
tetrakis(hydroxymethyl)phosphonium chloride

Test animals

Species:
other: rats and rabbits
Sex:
male
Details on test animals or test system and environmental conditions:
88 healthy male white rats of the same strain (bw: 250-300g) were used in a comparative assessment for 7 test items.
30 healthy male white rabbits of the same strain (bw: 3000g) were used in a comparative assessment for 7 test items.

Administration / exposure

Type of coverage:
not specified
Vehicle:
water
Details on exposure:
3 mm portion of the hair from its root was left.
rat: 15%/20%/30% aqueous solutions of THPC (rat: 0.75 ml were applied to 3x3 cm area), corresponding to 450/600/900 mg/kg bw/day (Bittner, CSPC, 1999))
rabbit: 15% and 30% aqueous solutions of THPC (rabbit: 1 ml were applied to 4x4 cm area), corresponding to 50 and 100 mg/kg bw/day (Bittner, CSPC, 1999)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
observation period = treatment period (20 days)
Frequency of treatment:
once a day for 20 consecutive days
No. of animals per sex per dose:
rats: 4 per dose group
rabbits: 2 per dose group
Control animals:
yes, concurrent vehicle
Details on study design:
Protocol amendment: Treatment with THPC were discontinued after day 8 (rats) or after day 6 (rabbit) because of local effects (redness) beginning on day 2 and marked body weight loss. Treated animals were necropsied on day 12 (rats).

Examinations

Observations and examinations performed and frequency:
Rat: Skin reactions beginning on day 2, intensifying till day 6. Falling-off of hair on day 7. The application in rats was discontinued on day 8, but all animals showed marked body weight loss and eventually died on day 9 (high dose group). Surviving animals were necropsied on day 12 (rats).
Rabbit: Redness of skin

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
Rat: Skin reactions beginning on day 2, intensifying till day 6. Falling-off of hair on day 7. The application in rats was discontinued on day 8, but all animals showed marked body weight loss and eventually died on day 9 (high dose group) and were necropsied on day 12 (rats).
Rabbit: Redness of skin on the 2nd day.
Histopathologic findings of the skin: Erythema and epidermal atrophy were observed when rats were treated with 15%, 20%, 30%aqueous THPC (450, 600, 900 mg/kg/day) for 8 days; and all rats of the highest dose group (30% THPC, 900 mg/kg) died after 9 days administration.
When rabbits were treated dermally with a 15% (50 mg/kg/day) THPC solution, severe redness was noted within 6 days; histopathological examination showed subepidermal fibrosis, without the regeneration of papillae, at the 30% concentration (100 mg/kg/day).

Effect levels

open allclose all
Dose descriptor:
LOAEL
Remarks:
rat, local
Effect level:
<= 15 mg/cm² per day
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: severe skin effects at site of contact.
Dose descriptor:
LOAEL
Remarks:
rat, systemic
Effect level:
<= 450 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: marked body weight loss, death of all high dose animals on day 9 (900 mg/kg bw/day)
Dose descriptor:
LOAEL
Remarks:
rabbit, local
Effect level:
<= 17 mg/cm² per day
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: severe skin effects at site of contact
Dose descriptor:
LOAEL
Remarks:
rabbit, systemic
Effect level:
<= 50 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: falling-off of hair, treatment discontinued after day 6

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Low dose groups (15% THPC) showed severe local effects in both rats and rabbits.