(S)-7-[[2-O-6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 15th to November 29th, 2016.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(S)-7-[[2-O-6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one

EC Number:

236-216-9

EC Name:

(S)-7-[[2-O-6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one

Cas Number:

13241-33-3

Molecular formula:

C28H34O15

IUPAC Name:

(S)-7-[[2-O-6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

(SPF Caw)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle – France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: the males were 7 weeks old and the females 8 weeks old.
- Weight at study initiation: the mean weight of male rats was 267.6 g, and the mean weight of female rats 222.0 g
- Housing: during the treatment, animals were kept in individual cages. They were solid-bottomed clear polycarbonate cages with a stainless steel mesh lid, containing dust free weed shavings (changed at least 2 times per week).
- Diet (e.g. ad libitum): foodstuff (ENVIGO 2016) ad libitum.
- Water (e.g. ad libitum): tap-water from public distribution system ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

DMSO

Details on dermal exposure:

TEST SITE
- % coverage: at least 10%
- Type of wrap if used: non occlusive porous gauze dressing (50 mm x 50 mm non woven swab of 4-layer patch from MEDISTOCK) secured in position with a strip of surgical adhesive tape (50 mm wides hypoallergenic microporeTM adhesive tape from 3M)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with distilled water.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 0.2 g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 ml/kg bw.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes

Remarks:

historical control.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systematic examinations were carried out daily to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. The animals were weighed on day 0 (just before administering the test item) then on day 2, day 7, and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (only if organs presenting abnormalities).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No systemic clinical signs related to the administration of the test item were observed.

Gross pathology:

The macroscopic examinations of the animals at the end of the study did not reveal treatment-related changes.

Other findings:

- Other observations: Erythema was noted in all animals (10/10) at 24 hours post dose. This reaction was totally reversible at day 3. Dryness of the skin was noted in females at day 2 and in all animals at day 3. The skin recovered a normal aspect on day 4. A yellow coloration was noted in all animals at 24 hours post-dose.

Any other information on results incl. tables

Table 1. Body weight evolution

Males	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rm 0689	266	268	2	317	51	401	135
Rm 0690	271	273	2	317	46	381	110
Rm 0691	271	271	0	327	56	379	108
Rm 0692	258	265	7	315	57	384	126
Rm 0693	272	276	4	333	61	379	107
Mean	267.6	270.6	3.0	321.8	54.2	384.8	117.2
SD	5.9	4.3	2.6	7.8	5.8	9.3	12.6
Females
Rm 0694	217	213	-4	242	25	259	42
Rm 0695	229	224	-5	258	29	274	45
Rm 0696	226	222	-4	253	27	270	44
Rm 0697	222	221	-1	247	25	279	57
Rm 0698	216	213	-3	239	23	283	67
Mean	222.0	218.6	-3.4	247.8	25.8	273.0	51.0
SD	5.6	5.2	1.5	7.8	2.3	9.2	10.7

 

Table 2. Necropsy data sheet.

Observations	Males Rm0689 to Rm0693	Females Rf0694 to Rf0698
General appearance	Normal	Normal
Oesophagus	NTR	NTR
Stomach	NTR	NTR
Duodenum	NTR	NTR
Jejunum	NTR	NTR
Ileon	NTR	NTR
Caecum	NTR	NTR
Colon	NTR	NTR
Rectum	NTR	NTR
Spleen	NTR	NTR
Liver	NTR	NTR
Thymus	NTR	NTR
Trachea	NTR	NTR
Lungs	NTR	NTR
Heart	NTR	NTR
Kidneys	NTR	NTR
Urinary bladder	NTR	NTR
Ovaries	-	NTR
Uterus	-	NTR
Testicles	NTR	-
Treatment area (skin)	NTR	NTR
Adrenals	NTR	NTR
Pancreas	NTR	NTR
Particulars	None	none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

EU criteria.

Conclusions:

The LD50 of the test item is higher than 2000 mg/kg body weight by dermal route in rats.

Executive summary:

The acute dermal toxicity of the test item was studied according to OECD 402 (GLP study). A limit test was performed by dermal administration of the test item at a dose of 2000 mg/kg bw to 5 male and 5 female Wistar (SPF:Caw) rats. After 24 h of exposure, the area was rinsed with water, and the animals were observed daily for 14 days. Observations included clinical signs, mortality, body weights, gross pathology and, if any abnormality was observed, histopathology of the affected tissues. No mortality or systemic clinical signs related to the administration of the test item were observed throughout the study. Erythema was noted in all animals (10/10) at 24 hours post dose. This reaction was totally reversible at day 3. Based on the results of the study, the test item was found to be non toxic, with an LD50 > 2000 mg/kg bw.